TBD Meeting (4970-17)

 

MELBOURNE – A metric for low disease activity in lupus is nearly ready for prime-time in both clinical practice and clinical trials, according to speakers at a recent international conference on systemic lupus erythematosus.

The Lupus Low Disease Activity State definition, developed by the Asia Pacific Lupus Collaboration, represents a state which, if sustained, is associated with a low likelihood of adverse outcome, said Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne.

Bianca Nogrady/Frontline Medical News

Dr. Nikpour told the conference that the diversity of clinical phenotypes in lupus and the presence of many disease activity measures has made the definition of active disease quite challenging.

“On the other hand, patients that are overall doing relatively well have less active disease and tend to look a little more homogeneous and potentially are easier to define,” Dr. Nikpour said. “If we’re able to define this group of patients who are doing well, that definition could potentially serve as a therapeutic target.”

The consensus definition of a Lupus Low Disease Activity State (LLDAS), contains five items. The first is that the patient must have a SLEDAI-2K score of less than or equal to 4, with no activity in major organs. Secondly, patients must show no new features of lupus activity, compared with the previous assessment. The third LLDAS item is a Physician Global Assessment score of 1 or less on a scale of 0 to 3. The fourth item is a current prednisolone or equivalent dose of 7.5 mg/day or less, and the fifth is that patients are on well-tolerated standard doses of immunosuppressants and approved biologic agents.

While the definition has been retrospectively validated, Dr. Nikpour presented data from a prospective study that examined the agreement between LLDAS and the clinical judgment of 50 lupus experts on 50 cases.

These data showed overall agreement between experts and LLDAS rating of remission or low, moderate, or high disease activity in 78% of cases.

“Where there were disagreements, when we looked at the cases in more detail, it really boiled down to whether the expert felt that serologic activity [such as] low complement/raised anti-dsDNA was important, and some experts also accepted prednisone doses up to 10 mg per day in what they thought would be a low disease activity state,” Dr. Nikpour said.

In the same session, Chak-Sing Lau, MBChB, MD, chair of rheumatology and clinical immunology at the University of Hong Kong, presented data from another prospective, cross-sectional validation study of the LLDAS measure in 339 lupus patients who were followed for 30 months.

This study showed that 92.6% of patients had ever achieved LLDAS during the study period, and 62.1% of patient days were spent in LLDAS. Researchers also found that patients who spent a higher percentage of time in LLDAS had a significantly lower incidence of flare, even after adjustment for gender and age.

Commenting on the study, Dr. Nikpour said LLDAS could be a feasible target for lupus – or at least part of one – and a therapeutic endpoint or outcome measure in clinical trials.

“We now have a prospective validation of LLDAS in the Asia Pacific cohort, again looking at protection against future flares, damage accrual, and perhaps even mortality, and a state which confers better health-related quality of life,” she said in an interview.

Bianca Nogrady/Frontline Medical News

In another presentation, Eric F. Morand, MD, PhD, head of the Monash Health Rheumatology Unit at Monash University, Melbourne, showed data from the phase IIb MUSE trial of the investigational drug anifrolumab, which suggested LLDAS also had utility as a clinical trial endpoint for lupus.

The study involved 305 patients with active disease who were randomized to standard of care plus 300 mg or 1,000 mg anifrolumab every 4 weeks, or placebo, with follow-up at 28 and 52 weeks.

The analysis showed that LLDAS was strongly associated with the trial’s primary endpoint of SRI-4 response plus a sustained reduction of oral corticosteroid dose to below 10 mg/day, although LLDAS also proved itself more stringent than the SRI-4 response criteria.

Similarly, LLDAS attainment was strongly associated with BILAG (British Isles Lupus Assessment Group)–Based Composite Lupus Assessment response but again, was more stringent. However LLDAS was less stringent than the major clinical response definition used in the study, which was BILAG ‘C’ or less across all systems for a minimum of 6 months.

Patients who achieved a low disease activity state at week 52 also showed significantly greater improvements in patient global score, and in seven of the eight lupus quality of life domains, compared with patients who did not achieve LLDAS.

“The purpose of this analysis is not to evaluate the efficacy of anifrolumab but rather to evaluate the utility of this measure, and we believe that this has been attained,” Dr. Morand told the audience.

In an interview, Dr. Morand said the accumulating evidence for the validity of LLDAS both in clinical trials and clinical practice was approaching a tipping point, with numerous presentations at the conference addressing the question of LLDAS.

“Of course those findings have to be peer reviewed and published, and probably it needs to be tested in another clinical trial or two and still hold water, but I think it’s got momentum now.”

Dr. Nikpour declared research support, honoraria, and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
 

 

[email protected]

 

MELBOURNE – A metric for low disease activity in lupus is nearly ready for prime-time in both clinical practice and clinical trials, according to speakers at a recent international conference on systemic lupus erythematosus.

The Lupus Low Disease Activity State definition, developed by the Asia Pacific Lupus Collaboration, represents a state which, if sustained, is associated with a low likelihood of adverse outcome, said Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne.

Bianca Nogrady/Frontline Medical News

Dr. Nikpour told the conference that the diversity of clinical phenotypes in lupus and the presence of many disease activity measures has made the definition of active disease quite challenging.

“On the other hand, patients that are overall doing relatively well have less active disease and tend to look a little more homogeneous and potentially are easier to define,” Dr. Nikpour said. “If we’re able to define this group of patients who are doing well, that definition could potentially serve as a therapeutic target.”

The consensus definition of a Lupus Low Disease Activity State (LLDAS), contains five items. The first is that the patient must have a SLEDAI-2K score of less than or equal to 4, with no activity in major organs. Secondly, patients must show no new features of lupus activity, compared with the previous assessment. The third LLDAS item is a Physician Global Assessment score of 1 or less on a scale of 0 to 3. The fourth item is a current prednisolone or equivalent dose of 7.5 mg/day or less, and the fifth is that patients are on well-tolerated standard doses of immunosuppressants and approved biologic agents.

While the definition has been retrospectively validated, Dr. Nikpour presented data from a prospective study that examined the agreement between LLDAS and the clinical judgment of 50 lupus experts on 50 cases.

These data showed overall agreement between experts and LLDAS rating of remission or low, moderate, or high disease activity in 78% of cases.

“Where there were disagreements, when we looked at the cases in more detail, it really boiled down to whether the expert felt that serologic activity [such as] low complement/raised anti-dsDNA was important, and some experts also accepted prednisone doses up to 10 mg per day in what they thought would be a low disease activity state,” Dr. Nikpour said.

In the same session, Chak-Sing Lau, MBChB, MD, chair of rheumatology and clinical immunology at the University of Hong Kong, presented data from another prospective, cross-sectional validation study of the LLDAS measure in 339 lupus patients who were followed for 30 months.

This study showed that 92.6% of patients had ever achieved LLDAS during the study period, and 62.1% of patient days were spent in LLDAS. Researchers also found that patients who spent a higher percentage of time in LLDAS had a significantly lower incidence of flare, even after adjustment for gender and age.

Commenting on the study, Dr. Nikpour said LLDAS could be a feasible target for lupus – or at least part of one – and a therapeutic endpoint or outcome measure in clinical trials.

“We now have a prospective validation of LLDAS in the Asia Pacific cohort, again looking at protection against future flares, damage accrual, and perhaps even mortality, and a state which confers better health-related quality of life,” she said in an interview.

Bianca Nogrady/Frontline Medical News

In another presentation, Eric F. Morand, MD, PhD, head of the Monash Health Rheumatology Unit at Monash University, Melbourne, showed data from the phase IIb MUSE trial of the investigational drug anifrolumab, which suggested LLDAS also had utility as a clinical trial endpoint for lupus.

The study involved 305 patients with active disease who were randomized to standard of care plus 300 mg or 1,000 mg anifrolumab every 4 weeks, or placebo, with follow-up at 28 and 52 weeks.

The analysis showed that LLDAS was strongly associated with the trial’s primary endpoint of SRI-4 response plus a sustained reduction of oral corticosteroid dose to below 10 mg/day, although LLDAS also proved itself more stringent than the SRI-4 response criteria.

Similarly, LLDAS attainment was strongly associated with BILAG (British Isles Lupus Assessment Group)–Based Composite Lupus Assessment response but again, was more stringent. However LLDAS was less stringent than the major clinical response definition used in the study, which was BILAG ‘C’ or less across all systems for a minimum of 6 months.

Patients who achieved a low disease activity state at week 52 also showed significantly greater improvements in patient global score, and in seven of the eight lupus quality of life domains, compared with patients who did not achieve LLDAS.

“The purpose of this analysis is not to evaluate the efficacy of anifrolumab but rather to evaluate the utility of this measure, and we believe that this has been attained,” Dr. Morand told the audience.

In an interview, Dr. Morand said the accumulating evidence for the validity of LLDAS both in clinical trials and clinical practice was approaching a tipping point, with numerous presentations at the conference addressing the question of LLDAS.

“Of course those findings have to be peer reviewed and published, and probably it needs to be tested in another clinical trial or two and still hold water, but I think it’s got momentum now.”

Dr. Nikpour declared research support, honoraria, and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
 

 

[email protected]

 

MELBOURNE – A metric for low disease activity in lupus is nearly ready for prime-time in both clinical practice and clinical trials, according to speakers at a recent international conference on systemic lupus erythematosus.

The Lupus Low Disease Activity State definition, developed by the Asia Pacific Lupus Collaboration, represents a state which, if sustained, is associated with a low likelihood of adverse outcome, said Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne.

Bianca Nogrady/Frontline Medical News

Dr. Nikpour told the conference that the diversity of clinical phenotypes in lupus and the presence of many disease activity measures has made the definition of active disease quite challenging.

“On the other hand, patients that are overall doing relatively well have less active disease and tend to look a little more homogeneous and potentially are easier to define,” Dr. Nikpour said. “If we’re able to define this group of patients who are doing well, that definition could potentially serve as a therapeutic target.”

The consensus definition of a Lupus Low Disease Activity State (LLDAS), contains five items. The first is that the patient must have a SLEDAI-2K score of less than or equal to 4, with no activity in major organs. Secondly, patients must show no new features of lupus activity, compared with the previous assessment. The third LLDAS item is a Physician Global Assessment score of 1 or less on a scale of 0 to 3. The fourth item is a current prednisolone or equivalent dose of 7.5 mg/day or less, and the fifth is that patients are on well-tolerated standard doses of immunosuppressants and approved biologic agents.

While the definition has been retrospectively validated, Dr. Nikpour presented data from a prospective study that examined the agreement between LLDAS and the clinical judgment of 50 lupus experts on 50 cases.

These data showed overall agreement between experts and LLDAS rating of remission or low, moderate, or high disease activity in 78% of cases.

“Where there were disagreements, when we looked at the cases in more detail, it really boiled down to whether the expert felt that serologic activity [such as] low complement/raised anti-dsDNA was important, and some experts also accepted prednisone doses up to 10 mg per day in what they thought would be a low disease activity state,” Dr. Nikpour said.

In the same session, Chak-Sing Lau, MBChB, MD, chair of rheumatology and clinical immunology at the University of Hong Kong, presented data from another prospective, cross-sectional validation study of the LLDAS measure in 339 lupus patients who were followed for 30 months.

This study showed that 92.6% of patients had ever achieved LLDAS during the study period, and 62.1% of patient days were spent in LLDAS. Researchers also found that patients who spent a higher percentage of time in LLDAS had a significantly lower incidence of flare, even after adjustment for gender and age.

Commenting on the study, Dr. Nikpour said LLDAS could be a feasible target for lupus – or at least part of one – and a therapeutic endpoint or outcome measure in clinical trials.

“We now have a prospective validation of LLDAS in the Asia Pacific cohort, again looking at protection against future flares, damage accrual, and perhaps even mortality, and a state which confers better health-related quality of life,” she said in an interview.

Bianca Nogrady/Frontline Medical News

In another presentation, Eric F. Morand, MD, PhD, head of the Monash Health Rheumatology Unit at Monash University, Melbourne, showed data from the phase IIb MUSE trial of the investigational drug anifrolumab, which suggested LLDAS also had utility as a clinical trial endpoint for lupus.

The study involved 305 patients with active disease who were randomized to standard of care plus 300 mg or 1,000 mg anifrolumab every 4 weeks, or placebo, with follow-up at 28 and 52 weeks.

The analysis showed that LLDAS was strongly associated with the trial’s primary endpoint of SRI-4 response plus a sustained reduction of oral corticosteroid dose to below 10 mg/day, although LLDAS also proved itself more stringent than the SRI-4 response criteria.

Similarly, LLDAS attainment was strongly associated with BILAG (British Isles Lupus Assessment Group)–Based Composite Lupus Assessment response but again, was more stringent. However LLDAS was less stringent than the major clinical response definition used in the study, which was BILAG ‘C’ or less across all systems for a minimum of 6 months.

Patients who achieved a low disease activity state at week 52 also showed significantly greater improvements in patient global score, and in seven of the eight lupus quality of life domains, compared with patients who did not achieve LLDAS.

“The purpose of this analysis is not to evaluate the efficacy of anifrolumab but rather to evaluate the utility of this measure, and we believe that this has been attained,” Dr. Morand told the audience.

In an interview, Dr. Morand said the accumulating evidence for the validity of LLDAS both in clinical trials and clinical practice was approaching a tipping point, with numerous presentations at the conference addressing the question of LLDAS.

“Of course those findings have to be peer reviewed and published, and probably it needs to be tested in another clinical trial or two and still hold water, but I think it’s got momentum now.”

Dr. Nikpour declared research support, honoraria, and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
 

 

[email protected]

 

MELBOURNE – Researchers have identified six microRNAs that may indicate a better likelihood of response to cyclophosphamide in patients with lupus nephritis, according to a study presented at an international conference on systemic lupus erythematosus.

“MicroRNA has been shown to be important in systemic lupus in several studies, and they’ve identified several microRNA that have been shown to affect the outcome measures in patients,” said Sarfaraz Hasni, MD, director of the Lupus Clinical Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., who presented a poster on the study at the meeting.

Bianca Nogrady/Frontline Medical News

Dr. Hasni said that microRNA, which are small, noncoding RNA that play a role in the regulation of gene expression, have also been shown to have altered expression levels in a variety of diseases.

The aim of this study, involving 71 patients with lupus nephritis, was to look for microRNAs associated with treatment response to cyclophosphamide.

The first stage of the study involved isolating microRNAs from kidney biopsies taken from a first cohort of 17 responders and 15 nonresponders.

Responders were patients who, after 2 years of intravenous cyclophosphamide, showed no active urinary sediments, less than five red blood cells or white blood cells in urine, and proteinuria below 1 g/24 hours.

After analyzing 300-400 microRNAs in these biopsies, the investigators identified 6 that were significantly upregulated in association with treatment outcome in both the first cohort as well as a second validation cohort of 22 responders and 17 nonresponders.

When the researchers looked at the most likely genetic targets of these microRNAs, they identified genes associated with G2/M DNA damage checkpoint regulation, which points to a link with cyclophosphamide efficacy, as well as associations with immunological disease and renal inflammation.

Dr. Hasni said that previous studies of microRNA had looked in the peripheral blood but suggested this may not necessarily reflect what was happening in the kidney.

The next step for researchers is to see if upregulation of these microRNAs is predictive of treatment response.

“If you are giving cyclophosphamide for 2 years, it comes with a high risk of side effects, especially in young women because there is potential for premature ovarian failure,” Dr. Hasni said in an interview. “If we can predict that this patient is not going to respond to cyclophosphamide or will not have a good outcome, we can use alternative therapy, or perhaps use more aggressive or a combination therapy approach rather than keep doing the same thing and 2 years later find out the patient is not going to respond.”

The researchers are also keen to investigate whether these same microRNAs can be isolated from serum or urine, which would reduce the need for kidney biopsy.

“The testing for microRNA is not that hard – it’s the biopsy and extracting the tissue from the biopsy... that’s obviously cumbersome and can only be done in a research setting.”

No conflicts of interest were declared.

 

MELBOURNE – Researchers have identified six microRNAs that may indicate a better likelihood of response to cyclophosphamide in patients with lupus nephritis, according to a study presented at an international conference on systemic lupus erythematosus.

“MicroRNA has been shown to be important in systemic lupus in several studies, and they’ve identified several microRNA that have been shown to affect the outcome measures in patients,” said Sarfaraz Hasni, MD, director of the Lupus Clinical Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., who presented a poster on the study at the meeting.

Bianca Nogrady/Frontline Medical News

Dr. Hasni said that microRNA, which are small, noncoding RNA that play a role in the regulation of gene expression, have also been shown to have altered expression levels in a variety of diseases.

The aim of this study, involving 71 patients with lupus nephritis, was to look for microRNAs associated with treatment response to cyclophosphamide.

The first stage of the study involved isolating microRNAs from kidney biopsies taken from a first cohort of 17 responders and 15 nonresponders.

Responders were patients who, after 2 years of intravenous cyclophosphamide, showed no active urinary sediments, less than five red blood cells or white blood cells in urine, and proteinuria below 1 g/24 hours.

After analyzing 300-400 microRNAs in these biopsies, the investigators identified 6 that were significantly upregulated in association with treatment outcome in both the first cohort as well as a second validation cohort of 22 responders and 17 nonresponders.

When the researchers looked at the most likely genetic targets of these microRNAs, they identified genes associated with G2/M DNA damage checkpoint regulation, which points to a link with cyclophosphamide efficacy, as well as associations with immunological disease and renal inflammation.

Dr. Hasni said that previous studies of microRNA had looked in the peripheral blood but suggested this may not necessarily reflect what was happening in the kidney.

The next step for researchers is to see if upregulation of these microRNAs is predictive of treatment response.

“If you are giving cyclophosphamide for 2 years, it comes with a high risk of side effects, especially in young women because there is potential for premature ovarian failure,” Dr. Hasni said in an interview. “If we can predict that this patient is not going to respond to cyclophosphamide or will not have a good outcome, we can use alternative therapy, or perhaps use more aggressive or a combination therapy approach rather than keep doing the same thing and 2 years later find out the patient is not going to respond.”

The researchers are also keen to investigate whether these same microRNAs can be isolated from serum or urine, which would reduce the need for kidney biopsy.

“The testing for microRNA is not that hard – it’s the biopsy and extracting the tissue from the biopsy... that’s obviously cumbersome and can only be done in a research setting.”

No conflicts of interest were declared.

 

MELBOURNE – Researchers have identified six microRNAs that may indicate a better likelihood of response to cyclophosphamide in patients with lupus nephritis, according to a study presented at an international conference on systemic lupus erythematosus.

“MicroRNA has been shown to be important in systemic lupus in several studies, and they’ve identified several microRNA that have been shown to affect the outcome measures in patients,” said Sarfaraz Hasni, MD, director of the Lupus Clinical Research Program at the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Md., who presented a poster on the study at the meeting.

Bianca Nogrady/Frontline Medical News

Dr. Hasni said that microRNA, which are small, noncoding RNA that play a role in the regulation of gene expression, have also been shown to have altered expression levels in a variety of diseases.

The aim of this study, involving 71 patients with lupus nephritis, was to look for microRNAs associated with treatment response to cyclophosphamide.

The first stage of the study involved isolating microRNAs from kidney biopsies taken from a first cohort of 17 responders and 15 nonresponders.

Responders were patients who, after 2 years of intravenous cyclophosphamide, showed no active urinary sediments, less than five red blood cells or white blood cells in urine, and proteinuria below 1 g/24 hours.

After analyzing 300-400 microRNAs in these biopsies, the investigators identified 6 that were significantly upregulated in association with treatment outcome in both the first cohort as well as a second validation cohort of 22 responders and 17 nonresponders.

When the researchers looked at the most likely genetic targets of these microRNAs, they identified genes associated with G2/M DNA damage checkpoint regulation, which points to a link with cyclophosphamide efficacy, as well as associations with immunological disease and renal inflammation.

Dr. Hasni said that previous studies of microRNA had looked in the peripheral blood but suggested this may not necessarily reflect what was happening in the kidney.

The next step for researchers is to see if upregulation of these microRNAs is predictive of treatment response.

“If you are giving cyclophosphamide for 2 years, it comes with a high risk of side effects, especially in young women because there is potential for premature ovarian failure,” Dr. Hasni said in an interview. “If we can predict that this patient is not going to respond to cyclophosphamide or will not have a good outcome, we can use alternative therapy, or perhaps use more aggressive or a combination therapy approach rather than keep doing the same thing and 2 years later find out the patient is not going to respond.”

The researchers are also keen to investigate whether these same microRNAs can be isolated from serum or urine, which would reduce the need for kidney biopsy.

“The testing for microRNA is not that hard – it’s the biopsy and extracting the tissue from the biopsy... that’s obviously cumbersome and can only be done in a research setting.”

No conflicts of interest were declared.

 

MELBOURNE – Two-thirds of patients with active systemic lupus erythematosus responded to treatment with belimumab at 2 years in a clinical practice setting, particularly those with higher disease activity or polyarthritis, according to data presented at an international conference on systemic lupus erythematosus.

In a multicenter prospective study of 188 patients with active systemic lupus erythematosus (SLE), Maddalena Larosa, MD, of the University of Padova (Italy) and her colleagues reported a 71.3% response rate with belimumab (Benlysta) at 12 months based on achieving SLE Responder Index (SRI-4) criteria. SRI-4 is a composite endpoint requiring at least a 4-point reduction in SLE Disease Activity Index 2000 (SLEDAI-2K) score, no worsening (less than 10-mm increase) from baseline in the Physician’s Global Assessment of Disease Activity score (PGA), and no new British Isles Lupus Assessment Group (BILAG) Domain A and no more than 1 new BILAG Domain B scores.

Bianca Nogrady/Frontline Medical News

The group had a 68.7% response rate at 24 months, which included 92% of the patients who responded at 12 months. Conversely, among nonresponders at 12 months, 87.5% of them still had not responded to the treatment by 24 months.

Patients were treated with belimumab as an add-on to standard care, with a treatment regimen of 10 mg/kg at day 0, 14, 28, and then every 28 days. The mean SLEDAI-2K score among patients was 8.3, all were positive for double-stranded DNA autoantibodies, and the mean Systemic Lupus International Collaborative Clinics (SLICC) Damage Index was 0.84. Nearly two-thirds of patients were also being treated with immunosuppressants.

Patients with a SLEDAI-2K score of 10 or above were 25 times more likely to respond by 12 months and 12 times more likely to respond by 24 months, both of which were statistically significant.

Similarly, patients with polyarthritis – who constituted nearly half of all patients in the study – were 8 times more likely to respond at 12 months, and 32 times more likely to respond at 24 months. Patients on a prednisone dose of 7.5 mg/day or greater were also significantly more likely to respond at 24 months.

“What was surprising in these patients who respond better are patients with higher disease activity,” Dr. Larosa said in an interview, noting that many patients had also had refractory disease.

Belimumab treatment was also associated with a plateauing of damage accrual, as measured by the SLICC Damage Index, she said.

“In the 5 years before belimumab initiation, we observed an increase of damage accrual related to SLE, but after the first belimumab infusion we did not observe any increase of damage accrual related to the disease,” Dr. Larosa told the audience.

The median duration of treatment was 12 months, but 58 patients (30.9%) discontinued belimumab, mainly because of adverse events. Eight patients also discontinued because of pregnancy, and two because of remission.

In response to a question on the effect of treatment on flare, Dr. Larosa said the treatment was also associated with a reduction in the number of patients who experienced flares, and a significant reduction in renal flares in patients with renal involvement.

No conflicts of interest were declared.

 

MELBOURNE – Two-thirds of patients with active systemic lupus erythematosus responded to treatment with belimumab at 2 years in a clinical practice setting, particularly those with higher disease activity or polyarthritis, according to data presented at an international conference on systemic lupus erythematosus.

In a multicenter prospective study of 188 patients with active systemic lupus erythematosus (SLE), Maddalena Larosa, MD, of the University of Padova (Italy) and her colleagues reported a 71.3% response rate with belimumab (Benlysta) at 12 months based on achieving SLE Responder Index (SRI-4) criteria. SRI-4 is a composite endpoint requiring at least a 4-point reduction in SLE Disease Activity Index 2000 (SLEDAI-2K) score, no worsening (less than 10-mm increase) from baseline in the Physician’s Global Assessment of Disease Activity score (PGA), and no new British Isles Lupus Assessment Group (BILAG) Domain A and no more than 1 new BILAG Domain B scores.

Bianca Nogrady/Frontline Medical News

The group had a 68.7% response rate at 24 months, which included 92% of the patients who responded at 12 months. Conversely, among nonresponders at 12 months, 87.5% of them still had not responded to the treatment by 24 months.

Patients were treated with belimumab as an add-on to standard care, with a treatment regimen of 10 mg/kg at day 0, 14, 28, and then every 28 days. The mean SLEDAI-2K score among patients was 8.3, all were positive for double-stranded DNA autoantibodies, and the mean Systemic Lupus International Collaborative Clinics (SLICC) Damage Index was 0.84. Nearly two-thirds of patients were also being treated with immunosuppressants.

Patients with a SLEDAI-2K score of 10 or above were 25 times more likely to respond by 12 months and 12 times more likely to respond by 24 months, both of which were statistically significant.

Similarly, patients with polyarthritis – who constituted nearly half of all patients in the study – were 8 times more likely to respond at 12 months, and 32 times more likely to respond at 24 months. Patients on a prednisone dose of 7.5 mg/day or greater were also significantly more likely to respond at 24 months.

“What was surprising in these patients who respond better are patients with higher disease activity,” Dr. Larosa said in an interview, noting that many patients had also had refractory disease.

Belimumab treatment was also associated with a plateauing of damage accrual, as measured by the SLICC Damage Index, she said.

“In the 5 years before belimumab initiation, we observed an increase of damage accrual related to SLE, but after the first belimumab infusion we did not observe any increase of damage accrual related to the disease,” Dr. Larosa told the audience.

The median duration of treatment was 12 months, but 58 patients (30.9%) discontinued belimumab, mainly because of adverse events. Eight patients also discontinued because of pregnancy, and two because of remission.

In response to a question on the effect of treatment on flare, Dr. Larosa said the treatment was also associated with a reduction in the number of patients who experienced flares, and a significant reduction in renal flares in patients with renal involvement.

No conflicts of interest were declared.

 

MELBOURNE – Two-thirds of patients with active systemic lupus erythematosus responded to treatment with belimumab at 2 years in a clinical practice setting, particularly those with higher disease activity or polyarthritis, according to data presented at an international conference on systemic lupus erythematosus.

In a multicenter prospective study of 188 patients with active systemic lupus erythematosus (SLE), Maddalena Larosa, MD, of the University of Padova (Italy) and her colleagues reported a 71.3% response rate with belimumab (Benlysta) at 12 months based on achieving SLE Responder Index (SRI-4) criteria. SRI-4 is a composite endpoint requiring at least a 4-point reduction in SLE Disease Activity Index 2000 (SLEDAI-2K) score, no worsening (less than 10-mm increase) from baseline in the Physician’s Global Assessment of Disease Activity score (PGA), and no new British Isles Lupus Assessment Group (BILAG) Domain A and no more than 1 new BILAG Domain B scores.

Bianca Nogrady/Frontline Medical News

The group had a 68.7% response rate at 24 months, which included 92% of the patients who responded at 12 months. Conversely, among nonresponders at 12 months, 87.5% of them still had not responded to the treatment by 24 months.

Patients were treated with belimumab as an add-on to standard care, with a treatment regimen of 10 mg/kg at day 0, 14, 28, and then every 28 days. The mean SLEDAI-2K score among patients was 8.3, all were positive for double-stranded DNA autoantibodies, and the mean Systemic Lupus International Collaborative Clinics (SLICC) Damage Index was 0.84. Nearly two-thirds of patients were also being treated with immunosuppressants.

Patients with a SLEDAI-2K score of 10 or above were 25 times more likely to respond by 12 months and 12 times more likely to respond by 24 months, both of which were statistically significant.

Similarly, patients with polyarthritis – who constituted nearly half of all patients in the study – were 8 times more likely to respond at 12 months, and 32 times more likely to respond at 24 months. Patients on a prednisone dose of 7.5 mg/day or greater were also significantly more likely to respond at 24 months.

“What was surprising in these patients who respond better are patients with higher disease activity,” Dr. Larosa said in an interview, noting that many patients had also had refractory disease.

Belimumab treatment was also associated with a plateauing of damage accrual, as measured by the SLICC Damage Index, she said.

“In the 5 years before belimumab initiation, we observed an increase of damage accrual related to SLE, but after the first belimumab infusion we did not observe any increase of damage accrual related to the disease,” Dr. Larosa told the audience.

The median duration of treatment was 12 months, but 58 patients (30.9%) discontinued belimumab, mainly because of adverse events. Eight patients also discontinued because of pregnancy, and two because of remission.

In response to a question on the effect of treatment on flare, Dr. Larosa said the treatment was also associated with a reduction in the number of patients who experienced flares, and a significant reduction in renal flares in patients with renal involvement.

No conflicts of interest were declared.

 

MELBOURNE – Adding a patient’s current dose of glucocorticoids as a new metric in the systemic lupus erythematosus disease activity index score could make it a better predictor of damage accrual, Dafna Gladman, MD, told an international congress on systemic lupus erythematosus.

Dr. Gladman and her colleagues from the University of Toronto Lupus Clinic at Toronto Western Hospital conducted a three-part study that aimed to incorporate glucocorticoid dose into the existing systemic lupus erythematosus disease activity index (SLEDAI)-2K score.

Bianca Nogrady/Frontline Medical News

“SLEDAI-2K is one of the most commonly used disease activity measures in lupus, both in clinical practice and research, but this index, as we all know, does not account for severity within an organ system,” Dr. Gladman told the conference.

“In clinical trials, the use of standard of care, which includes the use of corticosteroids, often confounds the results, and we see that in a number of trials, so there has been an unmet need to develop an index that incorporates the glucocorticoid dose into a disease activity measure.”

The first part of the study involved identification of 131 patient scenarios from a longitudinal cohort followed at the clinic for 20 years that included eight categories based on glucocorticoid dose, ranging from 5 to 60 mg/day.

In the second phase, three rheumatologists ranked the disease activity for each patient scenario using the Physician Global Assessment, and the study team used these rankings to derive a formula to explain the association between SLEDAI and glucocorticoid category.

The third phase used data from an inception cohort of patients from the clinic with 10 years of follow-up to validate the new score – called SLEDAI-2KG – by predicting the accrual of damage over the course of follow-up.

Researchers found that the modified score was significantly better at predicting damage accrual than was the original score.

“If somebody may have a very low disease activity measurable by the instrument, SLEDAI, but they’re still taking 10-15 mg prednisone, we need to somehow take it into account,” Dr. Gladman said in an interview. “It tells you that thinking that the patient is doing well but still taking 15 mg of prednisone is not appropriate.”

Session cochair Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne, questioned whether incorporating a treatment into a score for disease activity was too circular.

However, Dr. Gladman stressed that the glucocorticoid score was not based on what the physician planned to do, but what the patient was taking at the time of the consultation.

“If a patient has a rash and is currently taking 40 mg of prednisone, the value of the SLEDAI would be increased because of that dose,” she said. “On the other hand, somebody might come in with pleurisy, and some people might treat that with 60 mg, but they are only taking 20 mg; that suggests that the value would be lower in that particular patient.”

The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.

 

MELBOURNE – Adding a patient’s current dose of glucocorticoids as a new metric in the systemic lupus erythematosus disease activity index score could make it a better predictor of damage accrual, Dafna Gladman, MD, told an international congress on systemic lupus erythematosus.

Dr. Gladman and her colleagues from the University of Toronto Lupus Clinic at Toronto Western Hospital conducted a three-part study that aimed to incorporate glucocorticoid dose into the existing systemic lupus erythematosus disease activity index (SLEDAI)-2K score.

Bianca Nogrady/Frontline Medical News

“SLEDAI-2K is one of the most commonly used disease activity measures in lupus, both in clinical practice and research, but this index, as we all know, does not account for severity within an organ system,” Dr. Gladman told the conference.

“In clinical trials, the use of standard of care, which includes the use of corticosteroids, often confounds the results, and we see that in a number of trials, so there has been an unmet need to develop an index that incorporates the glucocorticoid dose into a disease activity measure.”

The first part of the study involved identification of 131 patient scenarios from a longitudinal cohort followed at the clinic for 20 years that included eight categories based on glucocorticoid dose, ranging from 5 to 60 mg/day.

In the second phase, three rheumatologists ranked the disease activity for each patient scenario using the Physician Global Assessment, and the study team used these rankings to derive a formula to explain the association between SLEDAI and glucocorticoid category.

The third phase used data from an inception cohort of patients from the clinic with 10 years of follow-up to validate the new score – called SLEDAI-2KG – by predicting the accrual of damage over the course of follow-up.

Researchers found that the modified score was significantly better at predicting damage accrual than was the original score.

“If somebody may have a very low disease activity measurable by the instrument, SLEDAI, but they’re still taking 10-15 mg prednisone, we need to somehow take it into account,” Dr. Gladman said in an interview. “It tells you that thinking that the patient is doing well but still taking 15 mg of prednisone is not appropriate.”

Session cochair Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne, questioned whether incorporating a treatment into a score for disease activity was too circular.

However, Dr. Gladman stressed that the glucocorticoid score was not based on what the physician planned to do, but what the patient was taking at the time of the consultation.

“If a patient has a rash and is currently taking 40 mg of prednisone, the value of the SLEDAI would be increased because of that dose,” she said. “On the other hand, somebody might come in with pleurisy, and some people might treat that with 60 mg, but they are only taking 20 mg; that suggests that the value would be lower in that particular patient.”

The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.

 

MELBOURNE – Adding a patient’s current dose of glucocorticoids as a new metric in the systemic lupus erythematosus disease activity index score could make it a better predictor of damage accrual, Dafna Gladman, MD, told an international congress on systemic lupus erythematosus.

Dr. Gladman and her colleagues from the University of Toronto Lupus Clinic at Toronto Western Hospital conducted a three-part study that aimed to incorporate glucocorticoid dose into the existing systemic lupus erythematosus disease activity index (SLEDAI)-2K score.

Bianca Nogrady/Frontline Medical News

“SLEDAI-2K is one of the most commonly used disease activity measures in lupus, both in clinical practice and research, but this index, as we all know, does not account for severity within an organ system,” Dr. Gladman told the conference.

“In clinical trials, the use of standard of care, which includes the use of corticosteroids, often confounds the results, and we see that in a number of trials, so there has been an unmet need to develop an index that incorporates the glucocorticoid dose into a disease activity measure.”

The first part of the study involved identification of 131 patient scenarios from a longitudinal cohort followed at the clinic for 20 years that included eight categories based on glucocorticoid dose, ranging from 5 to 60 mg/day.

In the second phase, three rheumatologists ranked the disease activity for each patient scenario using the Physician Global Assessment, and the study team used these rankings to derive a formula to explain the association between SLEDAI and glucocorticoid category.

The third phase used data from an inception cohort of patients from the clinic with 10 years of follow-up to validate the new score – called SLEDAI-2KG – by predicting the accrual of damage over the course of follow-up.

Researchers found that the modified score was significantly better at predicting damage accrual than was the original score.

“If somebody may have a very low disease activity measurable by the instrument, SLEDAI, but they’re still taking 10-15 mg prednisone, we need to somehow take it into account,” Dr. Gladman said in an interview. “It tells you that thinking that the patient is doing well but still taking 15 mg of prednisone is not appropriate.”

Session cochair Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne, questioned whether incorporating a treatment into a score for disease activity was too circular.

However, Dr. Gladman stressed that the glucocorticoid score was not based on what the physician planned to do, but what the patient was taking at the time of the consultation.

“If a patient has a rash and is currently taking 40 mg of prednisone, the value of the SLEDAI would be increased because of that dose,” she said. “On the other hand, somebody might come in with pleurisy, and some people might treat that with 60 mg, but they are only taking 20 mg; that suggests that the value would be lower in that particular patient.”

The study was supported by GlaxoSmithKline. Dr. Gladman and two coauthors declared receiving funding from GlaxoSmithKline.

 

MELBOURNE – Multidisciplinary management of comorbidities is one of the most important aspects of the care of patients with lupus nephritis, Frédéric Houssiau, MD, PhD, said at an international congress on systemic lupus erythematosus.

In his presentation describing his top 10 tips for the management of lupus nephritis, Dr. Houssiau said traditional risk factors do not explain the two- to threefold higher risk of cardiovascular disease in patients with lupus, making it important to address known cardiovascular disease risk factors.

Bianca Nogrady/Frontline Medical News

“So we should be spending time to tell our patients that they should stop smoking, they should undergo weight reduction, of course treat hypertension and LDL cholesterol with statins,” said Dr. Houssiau, head of the rheumatology department at the Cliniques Universitaires Saint-Luc and professor of rheumatology at the Université Catholique de Louvain, both in Brussels.

Dr. Houssiau also stressed the importance of paying attention to clotting disorders, preventing glucocorticoid-related intraocular pressure, ensuring patients are immunized against influenza, and enabling patient access to an intensive care unit in the event of severe sepsis.

He also called for physicians to “unmask” nonadherence to therapy, saying it was the most common cause of treatment failure.

“We don’t look enough to nonadherence to therapy, and we have no good clue to sort that out,” he said in an interview. “We can identify nonadherent patients, but it’s very difficult to change their mind, to make them adherent, and we have nurses, nurse-practitioners, questionnaires for adherence, but none of them, I think, so far have changed practice.”

Dr. Houssiau argued for the importance of having a good connection with a nephrologist and always performing a renal biopsy in patients with lupus nephritis.

“The reason for that is first to identify the immune deposits, either mesangial or subendothelial or subepithelial, and another reason is clearly not to miss the antiphospholipid syndrome,” he told the audience. “The third very good reason to perform the renal biopsy is clearly to classify the patient.”

Echoing other presentations at the conference, Dr. Houssiau said there was a need to define treatment targets in lupus nephritis.

“In diabetes, in hypertension, in rheumatoid arthritis, the target is well known by all of us,” he said. “What is the target that we should achieve in the lupus nephritis patient? That is much more difficult.”

He cited data from the recent MAINTAIN trial, which suggested that proteinuria levels at 12 months after initiation of treatment were highly predictive of patients who were likely to have a good renal prognosis. Patients with a 24-hour proteinuria level of around 0.7-0.8 g/day had a significantly greater likelihood of normal serum creatinine 7 years later, he said.

“Yet, we need more, we need better markers, because the negative predictive value is very bad, which means that a lot of patients who do not reach that target still, fortunately, will end up without renal failure.”

Dr. Houssiau also emphasized the need to minimize the use of steroids where possible, as data from an inception cohort run by him and his colleagues have shown that patients who failed to taper down to 4 mg of prednisone or less, after 1 year, had significantly more damage accrual.

He also advocated using either mycophenolate mofetil or intravenous cyclophosphamide as induction therapy based on data suggesting the two are equally efficacious at 6 months. Dr. Houssiau suggested favoring intravenous cyclophosphamide if fertility was a concern because it has been shown to not affect ovarian reserve and has the added advantage of better compliance.

Maintaining immunosuppression is also vital, Dr. Houssiau told the conference, and patients should be treated with immunosuppressants for at least 5, and possibly even up to 10, years.

“There is a small study showing an inverse correlation between the length of therapy and remission on the one hand, and risk of relapse, so the more you treat, the more the period of remission is long, the lower risk of relapse,” he said. However, there are little trial data on withdrawing immunosuppression or trials of immunosuppressant withdrawal, he noted.

Commenting on the future prospects for new treatments for lupus nephritis, Dr. Houssiau advised keeping faith in targeted therapies and precision medicine despite a slew of failed phase III clinical trials, and watching the development of calcineurin inhibitors, such as voclosporin.

Dr. Houssiau declared receiving research grants and honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Roche, Serono, and UCB.

 

MELBOURNE – Multidisciplinary management of comorbidities is one of the most important aspects of the care of patients with lupus nephritis, Frédéric Houssiau, MD, PhD, said at an international congress on systemic lupus erythematosus.

In his presentation describing his top 10 tips for the management of lupus nephritis, Dr. Houssiau said traditional risk factors do not explain the two- to threefold higher risk of cardiovascular disease in patients with lupus, making it important to address known cardiovascular disease risk factors.

Bianca Nogrady/Frontline Medical News

“So we should be spending time to tell our patients that they should stop smoking, they should undergo weight reduction, of course treat hypertension and LDL cholesterol with statins,” said Dr. Houssiau, head of the rheumatology department at the Cliniques Universitaires Saint-Luc and professor of rheumatology at the Université Catholique de Louvain, both in Brussels.

Dr. Houssiau also stressed the importance of paying attention to clotting disorders, preventing glucocorticoid-related intraocular pressure, ensuring patients are immunized against influenza, and enabling patient access to an intensive care unit in the event of severe sepsis.

He also called for physicians to “unmask” nonadherence to therapy, saying it was the most common cause of treatment failure.

“We don’t look enough to nonadherence to therapy, and we have no good clue to sort that out,” he said in an interview. “We can identify nonadherent patients, but it’s very difficult to change their mind, to make them adherent, and we have nurses, nurse-practitioners, questionnaires for adherence, but none of them, I think, so far have changed practice.”

Dr. Houssiau argued for the importance of having a good connection with a nephrologist and always performing a renal biopsy in patients with lupus nephritis.

“The reason for that is first to identify the immune deposits, either mesangial or subendothelial or subepithelial, and another reason is clearly not to miss the antiphospholipid syndrome,” he told the audience. “The third very good reason to perform the renal biopsy is clearly to classify the patient.”

Echoing other presentations at the conference, Dr. Houssiau said there was a need to define treatment targets in lupus nephritis.

“In diabetes, in hypertension, in rheumatoid arthritis, the target is well known by all of us,” he said. “What is the target that we should achieve in the lupus nephritis patient? That is much more difficult.”

He cited data from the recent MAINTAIN trial, which suggested that proteinuria levels at 12 months after initiation of treatment were highly predictive of patients who were likely to have a good renal prognosis. Patients with a 24-hour proteinuria level of around 0.7-0.8 g/day had a significantly greater likelihood of normal serum creatinine 7 years later, he said.

“Yet, we need more, we need better markers, because the negative predictive value is very bad, which means that a lot of patients who do not reach that target still, fortunately, will end up without renal failure.”

Dr. Houssiau also emphasized the need to minimize the use of steroids where possible, as data from an inception cohort run by him and his colleagues have shown that patients who failed to taper down to 4 mg of prednisone or less, after 1 year, had significantly more damage accrual.

He also advocated using either mycophenolate mofetil or intravenous cyclophosphamide as induction therapy based on data suggesting the two are equally efficacious at 6 months. Dr. Houssiau suggested favoring intravenous cyclophosphamide if fertility was a concern because it has been shown to not affect ovarian reserve and has the added advantage of better compliance.

Maintaining immunosuppression is also vital, Dr. Houssiau told the conference, and patients should be treated with immunosuppressants for at least 5, and possibly even up to 10, years.

“There is a small study showing an inverse correlation between the length of therapy and remission on the one hand, and risk of relapse, so the more you treat, the more the period of remission is long, the lower risk of relapse,” he said. However, there are little trial data on withdrawing immunosuppression or trials of immunosuppressant withdrawal, he noted.

Commenting on the future prospects for new treatments for lupus nephritis, Dr. Houssiau advised keeping faith in targeted therapies and precision medicine despite a slew of failed phase III clinical trials, and watching the development of calcineurin inhibitors, such as voclosporin.

Dr. Houssiau declared receiving research grants and honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Roche, Serono, and UCB.

 

MELBOURNE – Multidisciplinary management of comorbidities is one of the most important aspects of the care of patients with lupus nephritis, Frédéric Houssiau, MD, PhD, said at an international congress on systemic lupus erythematosus.

In his presentation describing his top 10 tips for the management of lupus nephritis, Dr. Houssiau said traditional risk factors do not explain the two- to threefold higher risk of cardiovascular disease in patients with lupus, making it important to address known cardiovascular disease risk factors.

Bianca Nogrady/Frontline Medical News

“So we should be spending time to tell our patients that they should stop smoking, they should undergo weight reduction, of course treat hypertension and LDL cholesterol with statins,” said Dr. Houssiau, head of the rheumatology department at the Cliniques Universitaires Saint-Luc and professor of rheumatology at the Université Catholique de Louvain, both in Brussels.

Dr. Houssiau also stressed the importance of paying attention to clotting disorders, preventing glucocorticoid-related intraocular pressure, ensuring patients are immunized against influenza, and enabling patient access to an intensive care unit in the event of severe sepsis.

He also called for physicians to “unmask” nonadherence to therapy, saying it was the most common cause of treatment failure.

“We don’t look enough to nonadherence to therapy, and we have no good clue to sort that out,” he said in an interview. “We can identify nonadherent patients, but it’s very difficult to change their mind, to make them adherent, and we have nurses, nurse-practitioners, questionnaires for adherence, but none of them, I think, so far have changed practice.”

Dr. Houssiau argued for the importance of having a good connection with a nephrologist and always performing a renal biopsy in patients with lupus nephritis.

“The reason for that is first to identify the immune deposits, either mesangial or subendothelial or subepithelial, and another reason is clearly not to miss the antiphospholipid syndrome,” he told the audience. “The third very good reason to perform the renal biopsy is clearly to classify the patient.”

Echoing other presentations at the conference, Dr. Houssiau said there was a need to define treatment targets in lupus nephritis.

“In diabetes, in hypertension, in rheumatoid arthritis, the target is well known by all of us,” he said. “What is the target that we should achieve in the lupus nephritis patient? That is much more difficult.”

He cited data from the recent MAINTAIN trial, which suggested that proteinuria levels at 12 months after initiation of treatment were highly predictive of patients who were likely to have a good renal prognosis. Patients with a 24-hour proteinuria level of around 0.7-0.8 g/day had a significantly greater likelihood of normal serum creatinine 7 years later, he said.

“Yet, we need more, we need better markers, because the negative predictive value is very bad, which means that a lot of patients who do not reach that target still, fortunately, will end up without renal failure.”

Dr. Houssiau also emphasized the need to minimize the use of steroids where possible, as data from an inception cohort run by him and his colleagues have shown that patients who failed to taper down to 4 mg of prednisone or less, after 1 year, had significantly more damage accrual.

He also advocated using either mycophenolate mofetil or intravenous cyclophosphamide as induction therapy based on data suggesting the two are equally efficacious at 6 months. Dr. Houssiau suggested favoring intravenous cyclophosphamide if fertility was a concern because it has been shown to not affect ovarian reserve and has the added advantage of better compliance.

Maintaining immunosuppression is also vital, Dr. Houssiau told the conference, and patients should be treated with immunosuppressants for at least 5, and possibly even up to 10, years.

“There is a small study showing an inverse correlation between the length of therapy and remission on the one hand, and risk of relapse, so the more you treat, the more the period of remission is long, the lower risk of relapse,” he said. However, there are little trial data on withdrawing immunosuppression or trials of immunosuppressant withdrawal, he noted.

Commenting on the future prospects for new treatments for lupus nephritis, Dr. Houssiau advised keeping faith in targeted therapies and precision medicine despite a slew of failed phase III clinical trials, and watching the development of calcineurin inhibitors, such as voclosporin.

Dr. Houssiau declared receiving research grants and honoraria from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Lilly, Roche, Serono, and UCB.

 

MELBOURNE – Vascular involvement in patients with lupus nephritis is associated with poorer outcomes and could be a trigger for a more aggressive treatment approach, according to observational study results reported at an international congress on systemic lupus erythematosus.

Manish Rathi, MD, a nephrologist at the Postgraduate Institution of Medical Education & Research in Chandigarh, India, reported the results of a 5-year prospective cohort study in 241 patients with biopsy-proven lupus nephritis.

Bianca Nogrady/Frontline Medical News

“There is emerging evidence that we should look into this compartment also when we talk about lupus nephritis,” Dr. Rathi told the conference. “The presence of vascular lesions are associated with greater severity of renal dysfunction and higher rates of progression to renal failure.”

Researchers found that patients with vascular involvement had significantly higher serum creatinine at baseline than did those without it. At follow-up, they also had significantly higher proteinuria and serum creatinine, as well as significantly lower serum albumin.

This group was also less likely to achieve complete remission, compared with patients without vascular involvement (38.2% vs. 61.9%; P = .006), and had treatment-refractory disease almost twice as often (26.3% vs. 14.3%; P = .02).

Overall, vascular involvement was seen in 32.3% of patients, with the most common form being arteriosclerosis (22.8%), followed by vascular thrombotic microangiopathy (11.2%), asymptomatic vascular immune deposits (5.3%), vasculopathy (2%), and vasculitis (0.8%).

Three-quarters of all patients had nephrotic syndrome, and 41.9% were identified as Class IV, 18.7% as Class V, 10.4% as Class III, and 3.7% as Class II.

When researchers examined the presentation and outcomes among these subgroups, they found that patients with vascular thrombotic microangiopathy had a significantly higher serum creatinine and were less likely to respond to treatment, compared with patients without vascular thrombotic microangiopathy (60% vs. 79.1%).

Similarly, patients with arteriosclerosis had significantly lower incidence of complete remission, compared with those without arteriosclerosis (37.7% vs. 58.8%) although they had significantly higher rates of partial remission (35.8% vs. 19.4%).

“Lupus patients, if they had involvement of vascular compartment, they had more severe presentation at the time of presentation as well as poorer outcomes despite giving the standard therapy,” Dr. Rathi said.

In an interview, Dr. Rathi said the results had already influenced their own treatment approach with these patients.

“What we have started doing now is – if there is vascular involvement, particularly the thrombotic microangiopathy – we treat them as severe lupus nephritis [patients], so even if their class of lupus nephritis is less severe, we’ll be treating them as severe,” he said.

Commenting on the presentation, Frederic Houssiau, MD, PhD, a professor of rheumatology at the Cliniques Universitaires Saint-Luc in Brussels, said he agreed that vascular involvement was neglected in the current classification of lupus nephritis and that it should be taken into account.

“Maybe we should not only consider the class but also look in more detail to the pathophysiological findings,” Dr. Houssiau said in an interview. “When you have a lot of inflammation in the vessels, for instance, maybe we should use cyclophosphamide.”

No conflicts of interest were disclosed.

 

MELBOURNE – Vascular involvement in patients with lupus nephritis is associated with poorer outcomes and could be a trigger for a more aggressive treatment approach, according to observational study results reported at an international congress on systemic lupus erythematosus.

Manish Rathi, MD, a nephrologist at the Postgraduate Institution of Medical Education & Research in Chandigarh, India, reported the results of a 5-year prospective cohort study in 241 patients with biopsy-proven lupus nephritis.

Bianca Nogrady/Frontline Medical News

“There is emerging evidence that we should look into this compartment also when we talk about lupus nephritis,” Dr. Rathi told the conference. “The presence of vascular lesions are associated with greater severity of renal dysfunction and higher rates of progression to renal failure.”

Researchers found that patients with vascular involvement had significantly higher serum creatinine at baseline than did those without it. At follow-up, they also had significantly higher proteinuria and serum creatinine, as well as significantly lower serum albumin.

This group was also less likely to achieve complete remission, compared with patients without vascular involvement (38.2% vs. 61.9%; P = .006), and had treatment-refractory disease almost twice as often (26.3% vs. 14.3%; P = .02).

Overall, vascular involvement was seen in 32.3% of patients, with the most common form being arteriosclerosis (22.8%), followed by vascular thrombotic microangiopathy (11.2%), asymptomatic vascular immune deposits (5.3%), vasculopathy (2%), and vasculitis (0.8%).

Three-quarters of all patients had nephrotic syndrome, and 41.9% were identified as Class IV, 18.7% as Class V, 10.4% as Class III, and 3.7% as Class II.

When researchers examined the presentation and outcomes among these subgroups, they found that patients with vascular thrombotic microangiopathy had a significantly higher serum creatinine and were less likely to respond to treatment, compared with patients without vascular thrombotic microangiopathy (60% vs. 79.1%).

Similarly, patients with arteriosclerosis had significantly lower incidence of complete remission, compared with those without arteriosclerosis (37.7% vs. 58.8%) although they had significantly higher rates of partial remission (35.8% vs. 19.4%).

“Lupus patients, if they had involvement of vascular compartment, they had more severe presentation at the time of presentation as well as poorer outcomes despite giving the standard therapy,” Dr. Rathi said.

In an interview, Dr. Rathi said the results had already influenced their own treatment approach with these patients.

“What we have started doing now is – if there is vascular involvement, particularly the thrombotic microangiopathy – we treat them as severe lupus nephritis [patients], so even if their class of lupus nephritis is less severe, we’ll be treating them as severe,” he said.

Commenting on the presentation, Frederic Houssiau, MD, PhD, a professor of rheumatology at the Cliniques Universitaires Saint-Luc in Brussels, said he agreed that vascular involvement was neglected in the current classification of lupus nephritis and that it should be taken into account.

“Maybe we should not only consider the class but also look in more detail to the pathophysiological findings,” Dr. Houssiau said in an interview. “When you have a lot of inflammation in the vessels, for instance, maybe we should use cyclophosphamide.”

No conflicts of interest were disclosed.

 

MELBOURNE – Vascular involvement in patients with lupus nephritis is associated with poorer outcomes and could be a trigger for a more aggressive treatment approach, according to observational study results reported at an international congress on systemic lupus erythematosus.

Manish Rathi, MD, a nephrologist at the Postgraduate Institution of Medical Education & Research in Chandigarh, India, reported the results of a 5-year prospective cohort study in 241 patients with biopsy-proven lupus nephritis.

Bianca Nogrady/Frontline Medical News

“There is emerging evidence that we should look into this compartment also when we talk about lupus nephritis,” Dr. Rathi told the conference. “The presence of vascular lesions are associated with greater severity of renal dysfunction and higher rates of progression to renal failure.”

Researchers found that patients with vascular involvement had significantly higher serum creatinine at baseline than did those without it. At follow-up, they also had significantly higher proteinuria and serum creatinine, as well as significantly lower serum albumin.

This group was also less likely to achieve complete remission, compared with patients without vascular involvement (38.2% vs. 61.9%; P = .006), and had treatment-refractory disease almost twice as often (26.3% vs. 14.3%; P = .02).

Overall, vascular involvement was seen in 32.3% of patients, with the most common form being arteriosclerosis (22.8%), followed by vascular thrombotic microangiopathy (11.2%), asymptomatic vascular immune deposits (5.3%), vasculopathy (2%), and vasculitis (0.8%).

Three-quarters of all patients had nephrotic syndrome, and 41.9% were identified as Class IV, 18.7% as Class V, 10.4% as Class III, and 3.7% as Class II.

When researchers examined the presentation and outcomes among these subgroups, they found that patients with vascular thrombotic microangiopathy had a significantly higher serum creatinine and were less likely to respond to treatment, compared with patients without vascular thrombotic microangiopathy (60% vs. 79.1%).

Similarly, patients with arteriosclerosis had significantly lower incidence of complete remission, compared with those without arteriosclerosis (37.7% vs. 58.8%) although they had significantly higher rates of partial remission (35.8% vs. 19.4%).

“Lupus patients, if they had involvement of vascular compartment, they had more severe presentation at the time of presentation as well as poorer outcomes despite giving the standard therapy,” Dr. Rathi said.

In an interview, Dr. Rathi said the results had already influenced their own treatment approach with these patients.

“What we have started doing now is – if there is vascular involvement, particularly the thrombotic microangiopathy – we treat them as severe lupus nephritis [patients], so even if their class of lupus nephritis is less severe, we’ll be treating them as severe,” he said.

Commenting on the presentation, Frederic Houssiau, MD, PhD, a professor of rheumatology at the Cliniques Universitaires Saint-Luc in Brussels, said he agreed that vascular involvement was neglected in the current classification of lupus nephritis and that it should be taken into account.

“Maybe we should not only consider the class but also look in more detail to the pathophysiological findings,” Dr. Houssiau said in an interview. “When you have a lot of inflammation in the vessels, for instance, maybe we should use cyclophosphamide.”

No conflicts of interest were disclosed.

 

MELBOURNE – A reduction in urinary protein creatinine ratio and normalization of inflammatory biomarkers early in treatment of lupus nephritis may predict response rates at 24 and 48 weeks, according to data from the AURION study presented at an international congress on systemic lupus erythematosus.

The AURION study was a single-arm exploratory study assessing the value of an early reduction in proteinuria in 10 patients with active lupus nephritis. The patients were treated with novel calcineurin inhibitor voclosporin (23.7 mg twice daily) in addition to usual care with mycophenolate mofetil and low-dose steroids. The treatment protocol also included a forced steroid taper from 0.5 g at day 0 to 2.5 mg from week 12.

The 48-week study examined the biomarkers of a 25% reduction in urinary protein creatinine ratio and normalization of inflammatory lupus biomarkers C3, C4, and anti–double stranded DNA at 8 weeks, and explored their relationship to remission rates at 24 and 48 weeks. Overall, by week 24, 70% of patients had achieved complete remission, and by week 48, 5 of 7 (71%) had achieved complete remission. Three patients dropped out of the study before week 48: one because of decreased estimated glomerular filtration rate, one because of a systemic lupus erythematosus flare, and one at the discretion of an investigator.

All patients showed a 25% reduction in urinary protein creatinine ratio at week 8, with a mean decrease of 61% by week 24. Researchers also saw a 22% increase in mean C3 levels and a 58% increase in mean C4 from baseline to week 24. There was also a decrease in anti–double stranded DNA.

When researchers examined the specificity and sensitivities of these biomarkers at week 8 in predicting renal response at weeks 24 and 48, they found that a 25% reduction in urinary protein creatinine ratio had a good sensitivity (71% and 75% at 24 and 48 weeks, respectively), but low specificity (33% and 24%).

In contrast, normalization of C4 and C3 by week 8 both showed a specificity of 100% by week 24 and 75% by week 48, but a sensitivity of 29% for week 24 and 25% for week 48.

Normalization of anti–double stranded DNA had a sensitivity of 57% at week 24 and 50% at week 48, and a specificity of 100% at week 24 and 50% at week 48.

Presenter Robert B. Huizinga, vice president of clinical affairs for Aurinia Pharmaceuticals, said the data showed there was unlikely to be one biomarker with both high sensitivity and high specificity.

“Certainly if you use C3, C4, and urinary protein creatinine ratio, you can say to the patient after week 8, ‘I don’t think this is going to work for you. You need to come off this therapy and move to something else,’ ” he said in an interview.

Mr. Huizinga said the company, which recently released 48-week data from the larger AURA-LV study of the same regimen in 265 patients, was now building this week-8 analysis into its studies, and hoped it would also provide an early predictive marker for other clinical trials.

Commenting on the findings, Brad Rovin, MD, professor of nephrology and pathology at Ohio State University, Columbus, and also an adviser to Aurinia, said this predictive ability would be extremely useful for clinicians.

“If a patient isn’t responding appropriately and you can really know that with some degree of certainty at 8 weeks, then instead of waiting 6 months to change therapy, maybe you should change earlier,” Dr. Rovin said in an interview.

This was particularly important in lupus nephritis, as the longer inflammation is allowed to continue, the greater the likelihood that it might tip over into fibrosis, he noted.

The study was funded by Aurinia.

 

MELBOURNE – A reduction in urinary protein creatinine ratio and normalization of inflammatory biomarkers early in treatment of lupus nephritis may predict response rates at 24 and 48 weeks, according to data from the AURION study presented at an international congress on systemic lupus erythematosus.

The AURION study was a single-arm exploratory study assessing the value of an early reduction in proteinuria in 10 patients with active lupus nephritis. The patients were treated with novel calcineurin inhibitor voclosporin (23.7 mg twice daily) in addition to usual care with mycophenolate mofetil and low-dose steroids. The treatment protocol also included a forced steroid taper from 0.5 g at day 0 to 2.5 mg from week 12.

The 48-week study examined the biomarkers of a 25% reduction in urinary protein creatinine ratio and normalization of inflammatory lupus biomarkers C3, C4, and anti–double stranded DNA at 8 weeks, and explored their relationship to remission rates at 24 and 48 weeks. Overall, by week 24, 70% of patients had achieved complete remission, and by week 48, 5 of 7 (71%) had achieved complete remission. Three patients dropped out of the study before week 48: one because of decreased estimated glomerular filtration rate, one because of a systemic lupus erythematosus flare, and one at the discretion of an investigator.

All patients showed a 25% reduction in urinary protein creatinine ratio at week 8, with a mean decrease of 61% by week 24. Researchers also saw a 22% increase in mean C3 levels and a 58% increase in mean C4 from baseline to week 24. There was also a decrease in anti–double stranded DNA.

When researchers examined the specificity and sensitivities of these biomarkers at week 8 in predicting renal response at weeks 24 and 48, they found that a 25% reduction in urinary protein creatinine ratio had a good sensitivity (71% and 75% at 24 and 48 weeks, respectively), but low specificity (33% and 24%).

In contrast, normalization of C4 and C3 by week 8 both showed a specificity of 100% by week 24 and 75% by week 48, but a sensitivity of 29% for week 24 and 25% for week 48.

Normalization of anti–double stranded DNA had a sensitivity of 57% at week 24 and 50% at week 48, and a specificity of 100% at week 24 and 50% at week 48.

Presenter Robert B. Huizinga, vice president of clinical affairs for Aurinia Pharmaceuticals, said the data showed there was unlikely to be one biomarker with both high sensitivity and high specificity.

“Certainly if you use C3, C4, and urinary protein creatinine ratio, you can say to the patient after week 8, ‘I don’t think this is going to work for you. You need to come off this therapy and move to something else,’ ” he said in an interview.

Mr. Huizinga said the company, which recently released 48-week data from the larger AURA-LV study of the same regimen in 265 patients, was now building this week-8 analysis into its studies, and hoped it would also provide an early predictive marker for other clinical trials.

Commenting on the findings, Brad Rovin, MD, professor of nephrology and pathology at Ohio State University, Columbus, and also an adviser to Aurinia, said this predictive ability would be extremely useful for clinicians.

“If a patient isn’t responding appropriately and you can really know that with some degree of certainty at 8 weeks, then instead of waiting 6 months to change therapy, maybe you should change earlier,” Dr. Rovin said in an interview.

This was particularly important in lupus nephritis, as the longer inflammation is allowed to continue, the greater the likelihood that it might tip over into fibrosis, he noted.

The study was funded by Aurinia.

 

MELBOURNE – A reduction in urinary protein creatinine ratio and normalization of inflammatory biomarkers early in treatment of lupus nephritis may predict response rates at 24 and 48 weeks, according to data from the AURION study presented at an international congress on systemic lupus erythematosus.

The AURION study was a single-arm exploratory study assessing the value of an early reduction in proteinuria in 10 patients with active lupus nephritis. The patients were treated with novel calcineurin inhibitor voclosporin (23.7 mg twice daily) in addition to usual care with mycophenolate mofetil and low-dose steroids. The treatment protocol also included a forced steroid taper from 0.5 g at day 0 to 2.5 mg from week 12.

The 48-week study examined the biomarkers of a 25% reduction in urinary protein creatinine ratio and normalization of inflammatory lupus biomarkers C3, C4, and anti–double stranded DNA at 8 weeks, and explored their relationship to remission rates at 24 and 48 weeks. Overall, by week 24, 70% of patients had achieved complete remission, and by week 48, 5 of 7 (71%) had achieved complete remission. Three patients dropped out of the study before week 48: one because of decreased estimated glomerular filtration rate, one because of a systemic lupus erythematosus flare, and one at the discretion of an investigator.

All patients showed a 25% reduction in urinary protein creatinine ratio at week 8, with a mean decrease of 61% by week 24. Researchers also saw a 22% increase in mean C3 levels and a 58% increase in mean C4 from baseline to week 24. There was also a decrease in anti–double stranded DNA.

When researchers examined the specificity and sensitivities of these biomarkers at week 8 in predicting renal response at weeks 24 and 48, they found that a 25% reduction in urinary protein creatinine ratio had a good sensitivity (71% and 75% at 24 and 48 weeks, respectively), but low specificity (33% and 24%).

In contrast, normalization of C4 and C3 by week 8 both showed a specificity of 100% by week 24 and 75% by week 48, but a sensitivity of 29% for week 24 and 25% for week 48.

Normalization of anti–double stranded DNA had a sensitivity of 57% at week 24 and 50% at week 48, and a specificity of 100% at week 24 and 50% at week 48.

Presenter Robert B. Huizinga, vice president of clinical affairs for Aurinia Pharmaceuticals, said the data showed there was unlikely to be one biomarker with both high sensitivity and high specificity.

“Certainly if you use C3, C4, and urinary protein creatinine ratio, you can say to the patient after week 8, ‘I don’t think this is going to work for you. You need to come off this therapy and move to something else,’ ” he said in an interview.

Mr. Huizinga said the company, which recently released 48-week data from the larger AURA-LV study of the same regimen in 265 patients, was now building this week-8 analysis into its studies, and hoped it would also provide an early predictive marker for other clinical trials.

Commenting on the findings, Brad Rovin, MD, professor of nephrology and pathology at Ohio State University, Columbus, and also an adviser to Aurinia, said this predictive ability would be extremely useful for clinicians.

“If a patient isn’t responding appropriately and you can really know that with some degree of certainty at 8 weeks, then instead of waiting 6 months to change therapy, maybe you should change earlier,” Dr. Rovin said in an interview.

This was particularly important in lupus nephritis, as the longer inflammation is allowed to continue, the greater the likelihood that it might tip over into fibrosis, he noted.

The study was funded by Aurinia.

 

MELBOURNE – SPECT imaging can identify abnormalities in brain perfusion in patients with multiple antiphospholipid antibodies and neuropsychiatric symptoms, but without a history of thrombosis, according to a study presented at an international congress on systemic lupus erythematosus.

The retrospective study by researchers from National Taiwan University Hospital addresses the challenge posed by patients who have antiphospholipid antibodies and neuropsychiatric symptoms but do not meet the full criteria for antiphospholipid syndrome because of a lack of a history of thromboembolism. Current antiphospholipid syndrome classification criteria are based on thrombosis or pregnancy loss, with a third category of noncriteria manifestations that include a range of neuropsychiatric symptoms, said presenter Ting-Syuan Lin, MD, of the Yun-Lin Branch of National Taiwan University Hospital.

Based on the study’s findings. Dr. Lin said that if patients did not show any abnormalities on CT scanning or MRI, SPECT imaging might be suitable to investigate for problems with perfusion.

“Some physicians may not give the patient early treatment because they do not fill the criteria,” Dr. Lin said in an interview. “But if we have SPECT image to document the abnormality, then the physician can have more confidence to give them early treatment.”

Dr. Lin and his colleagues looked at the brain SPECT images of 54 patients with a history of positive antiphospholipid antibodies and neuropsychiatric symptoms, but who had no history of thromboembolism or other lupus-related antibodies such as antibodies to double-stranded DNA. When the researchers looked simply at mean brain perfusion according to the number of antiphospholipid antibodies each patient had, they found no significant differences between the groups, including a control group of six patients without antiphospholipid antibodies.

But when they examined heterogeneity of brain perfusion, they saw significantly greater heterogeneity (P = .01) in patients with four antiphospholipid antibodies compared with patients who had no antibodies.

The patients enrolled in the study presented with a range of neuropsychiatric symptoms. The most common was headache (56.7%), followed by dizziness (41.7%), depression (28.3%), psychosis (15%), vertigo (8.3%), and seizures (6.7%). The mean age of the patients was 38 years, and 52 of the patients were women.

One of the patients – a 39-year-old woman with more than four antiphospholipid antibodies – had a normal CT scan but showed significant heterogeneity in brain perfusion on the SPECT imaging. She experienced a stroke 1 year after the study.

Commenting on the presentation, session cochair Timothy Godfrey, MBBS, of St. Vincent’s Hospital in Melbourne, said neuropsychiatric lupus was particularly problematic, especially when patients had normal imaging.

“You’re wondering is the patient just depressed or is there some other explanation, or do they truly have a manifestation of lupus which may require immunosuppression or anticoagulation?” he said in an interview.

This study “is highlighting the fact that maybe we do need to do these tests when the MRI is normal, particularly in people that have documented abnormalities in their blood test.”

Dr. Lin said the next phase of the study would look at whether treatment was associated with changes in brain perfusion on SPECT, and whether the abnormality of the SPECT imaging correlated with clinical outcomes.

No conflicts of interest were declared.

 

MELBOURNE – SPECT imaging can identify abnormalities in brain perfusion in patients with multiple antiphospholipid antibodies and neuropsychiatric symptoms, but without a history of thrombosis, according to a study presented at an international congress on systemic lupus erythematosus.

The retrospective study by researchers from National Taiwan University Hospital addresses the challenge posed by patients who have antiphospholipid antibodies and neuropsychiatric symptoms but do not meet the full criteria for antiphospholipid syndrome because of a lack of a history of thromboembolism. Current antiphospholipid syndrome classification criteria are based on thrombosis or pregnancy loss, with a third category of noncriteria manifestations that include a range of neuropsychiatric symptoms, said presenter Ting-Syuan Lin, MD, of the Yun-Lin Branch of National Taiwan University Hospital.

Based on the study’s findings. Dr. Lin said that if patients did not show any abnormalities on CT scanning or MRI, SPECT imaging might be suitable to investigate for problems with perfusion.

“Some physicians may not give the patient early treatment because they do not fill the criteria,” Dr. Lin said in an interview. “But if we have SPECT image to document the abnormality, then the physician can have more confidence to give them early treatment.”

Dr. Lin and his colleagues looked at the brain SPECT images of 54 patients with a history of positive antiphospholipid antibodies and neuropsychiatric symptoms, but who had no history of thromboembolism or other lupus-related antibodies such as antibodies to double-stranded DNA. When the researchers looked simply at mean brain perfusion according to the number of antiphospholipid antibodies each patient had, they found no significant differences between the groups, including a control group of six patients without antiphospholipid antibodies.

But when they examined heterogeneity of brain perfusion, they saw significantly greater heterogeneity (P = .01) in patients with four antiphospholipid antibodies compared with patients who had no antibodies.

The patients enrolled in the study presented with a range of neuropsychiatric symptoms. The most common was headache (56.7%), followed by dizziness (41.7%), depression (28.3%), psychosis (15%), vertigo (8.3%), and seizures (6.7%). The mean age of the patients was 38 years, and 52 of the patients were women.

One of the patients – a 39-year-old woman with more than four antiphospholipid antibodies – had a normal CT scan but showed significant heterogeneity in brain perfusion on the SPECT imaging. She experienced a stroke 1 year after the study.

Commenting on the presentation, session cochair Timothy Godfrey, MBBS, of St. Vincent’s Hospital in Melbourne, said neuropsychiatric lupus was particularly problematic, especially when patients had normal imaging.

“You’re wondering is the patient just depressed or is there some other explanation, or do they truly have a manifestation of lupus which may require immunosuppression or anticoagulation?” he said in an interview.

This study “is highlighting the fact that maybe we do need to do these tests when the MRI is normal, particularly in people that have documented abnormalities in their blood test.”

Dr. Lin said the next phase of the study would look at whether treatment was associated with changes in brain perfusion on SPECT, and whether the abnormality of the SPECT imaging correlated with clinical outcomes.

No conflicts of interest were declared.

 

MELBOURNE – SPECT imaging can identify abnormalities in brain perfusion in patients with multiple antiphospholipid antibodies and neuropsychiatric symptoms, but without a history of thrombosis, according to a study presented at an international congress on systemic lupus erythematosus.

The retrospective study by researchers from National Taiwan University Hospital addresses the challenge posed by patients who have antiphospholipid antibodies and neuropsychiatric symptoms but do not meet the full criteria for antiphospholipid syndrome because of a lack of a history of thromboembolism. Current antiphospholipid syndrome classification criteria are based on thrombosis or pregnancy loss, with a third category of noncriteria manifestations that include a range of neuropsychiatric symptoms, said presenter Ting-Syuan Lin, MD, of the Yun-Lin Branch of National Taiwan University Hospital.

Based on the study’s findings. Dr. Lin said that if patients did not show any abnormalities on CT scanning or MRI, SPECT imaging might be suitable to investigate for problems with perfusion.

“Some physicians may not give the patient early treatment because they do not fill the criteria,” Dr. Lin said in an interview. “But if we have SPECT image to document the abnormality, then the physician can have more confidence to give them early treatment.”

Dr. Lin and his colleagues looked at the brain SPECT images of 54 patients with a history of positive antiphospholipid antibodies and neuropsychiatric symptoms, but who had no history of thromboembolism or other lupus-related antibodies such as antibodies to double-stranded DNA. When the researchers looked simply at mean brain perfusion according to the number of antiphospholipid antibodies each patient had, they found no significant differences between the groups, including a control group of six patients without antiphospholipid antibodies.

But when they examined heterogeneity of brain perfusion, they saw significantly greater heterogeneity (P = .01) in patients with four antiphospholipid antibodies compared with patients who had no antibodies.

The patients enrolled in the study presented with a range of neuropsychiatric symptoms. The most common was headache (56.7%), followed by dizziness (41.7%), depression (28.3%), psychosis (15%), vertigo (8.3%), and seizures (6.7%). The mean age of the patients was 38 years, and 52 of the patients were women.

One of the patients – a 39-year-old woman with more than four antiphospholipid antibodies – had a normal CT scan but showed significant heterogeneity in brain perfusion on the SPECT imaging. She experienced a stroke 1 year after the study.

Commenting on the presentation, session cochair Timothy Godfrey, MBBS, of St. Vincent’s Hospital in Melbourne, said neuropsychiatric lupus was particularly problematic, especially when patients had normal imaging.

“You’re wondering is the patient just depressed or is there some other explanation, or do they truly have a manifestation of lupus which may require immunosuppression or anticoagulation?” he said in an interview.

This study “is highlighting the fact that maybe we do need to do these tests when the MRI is normal, particularly in people that have documented abnormalities in their blood test.”

Dr. Lin said the next phase of the study would look at whether treatment was associated with changes in brain perfusion on SPECT, and whether the abnormality of the SPECT imaging correlated with clinical outcomes.

No conflicts of interest were declared.