Michele G. Sullivan

COPENHAGEN – A test that measures how well patients recognize scents was highly correlated with progression from mild cognitive impairment to Alzheimer’s disease as well as neurodegeneration and beta-amyloid deposition in the brain in two separate studies.

Although the test is not ready for use in the clinic, it has the potential to be part of a panel of screening tests to predict the development of Alzheimer’s disease, researchers said at a press briefing during the Alzheimer’s Association International Conference 2014.

© Siri Stafford/Thinkstock

Timely detection of asymptomatic patients is currently lacking, said Dr. David S. Knopman, who moderated the session.

"Our principal clinical tools, including PET and MRI imaging, are excellent, but they are of little value for detecting patients in the preclinical stage of the disease," said Dr. Knopman, professor of neurology at the Mayo Clinic, Rochester, Minn. "These tests, on the other hand, are much simpler, less expensive and invasive, and would be feasible to use in the field, as opposed to only in a large research center."

The studies used the 40-item University of Pennsylvania Smell Identification Test (UPSIT), a scratch-and-sniff test that measures anosmia of mild, moderate, or severe levels, and costs about $25. For patients with Alzheimer’s disease, the test is a measure of memory, revealing an inability to recall once-familiar scent associations.

In one study, Matthew Growdon, a fourth-year medical student at Harvard University, Boston, and his colleagues found a significant relationship between olfactory impairment and pathologic markers of Alzheimer’s disease. The study involved 212 participants of the ongoing Harvard Aging Brain Study, which seeks to identify structural brain changes associated with memory impairment in aging. Participants were cognitively and physically healthy at baseline.

The investigators administered the UPSIT to all subjects, who also underwent a full evaluation to detect signs and symptoms of Alzheimer’s disease. The evaluation included cognitive testing, structural brain scanning, and amyloid imaging, as well as genetic testing and obtaining blood and spinal fluid biomarkers.

A linear regression model evaluated associations between the UPSIT and amyloid burden, hippocampal size, and thinning of the entorhinal cortex. A separate model looked at associations between UPSIT scores and memory test results.

A total of 100 participants were high performers, scoring in the upper 75th percentile of both the UPSIT and the memory tests. The remaining 112 were considered low performers. Of these, 59 scored in the lower 25th percentile of the UPSIT, but in the upper 25th percentile of memory. Nineteen scored in the upper 75th percentile of the UPSIT but the lower 25th percentile of memory, and 34 in the lower 25th percentile of both the UPSIT and memory.

The investigators found a linear correlation between poor UPSIT performance and both lower hippocampal volume on MRI and higher amyloid burden based on Pittsburgh compound B PET imaging. There was a marginal association between poorer UPSIT scores and entorhinal cortex thinning, Mr. Growdon noted.

The associations may indicate that Alzheimer’s pathology affects neurons in the olfactory bulb as well as other brain regions, said Mr. Growdon. "We seem to be looking at neuronal death in all these regions. And what’s really interesting is that this could be the basis of a very simple, low-cost screening tool for a clinically normal, asymptomatic older population. I envision it as something that could flag those at risk of developing symptoms or as a gateway to more expensive or invasive testing.

"It’s not ready for prime-time, though. This is a snapshot of a single moment in time. We would need longitudinal studies before it could be incorporated into care – maybe as part of a panel of screening tests," he said.

Dr. Davangere Devanand presented a second, unrelated study in which he and his colleagues measured the association between olfactory identification impairment and progression from mild cognitive impairment to Alzheimer’s dementia.

The investigation followed 757 participants of the Northern Manhattan Study, a multiethnic community sample in New York that has been used in large part to examine stroke risk factors. The participants initially took the UPSIT during 2004-2006, followed by additional testing during 2006-2008 and 2008-2010.

A total of 109 transitioned from normal cognition to mild cognitive impairment, and then 101 progressed to Alzheimer’s disease.

A low score on the UPSIT test significantly predicted the development of Alzheimer’s with a specificity of 65%. For each one-point decline in UPSIT score, the risk of developing Alzheimer’s increased by 5%.

The specificity of a low score on the UPSIT improved significantly to 77% when combined with the Selective Reminding Test immediate recall subscore. Even alone, the olfactory test was a better predictor of Alzheimer’s than was the memory test, said Dr. Devanand, director of the division of geriatric psychiatry and professor of psychiatry and neurology at Columbia University, New York.

Dr. Devanand said this test would also require further study before it could be incorporated into clinical practice. "We think of this not as a gold standard test, but as one we would add to other tests in making a prediction."

The Harvard Aging Brain Study is funded by the National Institute on Aging. The Northern Manhattan Study is funded by the National Institute of Neurological Disorders and Stroke. Neither Mr. Growdon nor Dr. Devanand had any relevant financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – A test that measures how well patients recognize scents was highly correlated with progression from mild cognitive impairment to Alzheimer’s disease as well as neurodegeneration and beta-amyloid deposition in the brain in two separate studies.

Although the test is not ready for use in the clinic, it has the potential to be part of a panel of screening tests to predict the development of Alzheimer’s disease, researchers said at a press briefing during the Alzheimer’s Association International Conference 2014.

© Siri Stafford/Thinkstock

Timely detection of asymptomatic patients is currently lacking, said Dr. David S. Knopman, who moderated the session.

"Our principal clinical tools, including PET and MRI imaging, are excellent, but they are of little value for detecting patients in the preclinical stage of the disease," said Dr. Knopman, professor of neurology at the Mayo Clinic, Rochester, Minn. "These tests, on the other hand, are much simpler, less expensive and invasive, and would be feasible to use in the field, as opposed to only in a large research center."

The studies used the 40-item University of Pennsylvania Smell Identification Test (UPSIT), a scratch-and-sniff test that measures anosmia of mild, moderate, or severe levels, and costs about $25. For patients with Alzheimer’s disease, the test is a measure of memory, revealing an inability to recall once-familiar scent associations.

In one study, Matthew Growdon, a fourth-year medical student at Harvard University, Boston, and his colleagues found a significant relationship between olfactory impairment and pathologic markers of Alzheimer’s disease. The study involved 212 participants of the ongoing Harvard Aging Brain Study, which seeks to identify structural brain changes associated with memory impairment in aging. Participants were cognitively and physically healthy at baseline.

The investigators administered the UPSIT to all subjects, who also underwent a full evaluation to detect signs and symptoms of Alzheimer’s disease. The evaluation included cognitive testing, structural brain scanning, and amyloid imaging, as well as genetic testing and obtaining blood and spinal fluid biomarkers.

A linear regression model evaluated associations between the UPSIT and amyloid burden, hippocampal size, and thinning of the entorhinal cortex. A separate model looked at associations between UPSIT scores and memory test results.

A total of 100 participants were high performers, scoring in the upper 75th percentile of both the UPSIT and the memory tests. The remaining 112 were considered low performers. Of these, 59 scored in the lower 25th percentile of the UPSIT, but in the upper 25th percentile of memory. Nineteen scored in the upper 75th percentile of the UPSIT but the lower 25th percentile of memory, and 34 in the lower 25th percentile of both the UPSIT and memory.

The investigators found a linear correlation between poor UPSIT performance and both lower hippocampal volume on MRI and higher amyloid burden based on Pittsburgh compound B PET imaging. There was a marginal association between poorer UPSIT scores and entorhinal cortex thinning, Mr. Growdon noted.

The associations may indicate that Alzheimer’s pathology affects neurons in the olfactory bulb as well as other brain regions, said Mr. Growdon. "We seem to be looking at neuronal death in all these regions. And what’s really interesting is that this could be the basis of a very simple, low-cost screening tool for a clinically normal, asymptomatic older population. I envision it as something that could flag those at risk of developing symptoms or as a gateway to more expensive or invasive testing.

"It’s not ready for prime-time, though. This is a snapshot of a single moment in time. We would need longitudinal studies before it could be incorporated into care – maybe as part of a panel of screening tests," he said.

Dr. Davangere Devanand presented a second, unrelated study in which he and his colleagues measured the association between olfactory identification impairment and progression from mild cognitive impairment to Alzheimer’s dementia.

The investigation followed 757 participants of the Northern Manhattan Study, a multiethnic community sample in New York that has been used in large part to examine stroke risk factors. The participants initially took the UPSIT during 2004-2006, followed by additional testing during 2006-2008 and 2008-2010.

A total of 109 transitioned from normal cognition to mild cognitive impairment, and then 101 progressed to Alzheimer’s disease.

A low score on the UPSIT test significantly predicted the development of Alzheimer’s with a specificity of 65%. For each one-point decline in UPSIT score, the risk of developing Alzheimer’s increased by 5%.

The specificity of a low score on the UPSIT improved significantly to 77% when combined with the Selective Reminding Test immediate recall subscore. Even alone, the olfactory test was a better predictor of Alzheimer’s than was the memory test, said Dr. Devanand, director of the division of geriatric psychiatry and professor of psychiatry and neurology at Columbia University, New York.

Dr. Devanand said this test would also require further study before it could be incorporated into clinical practice. "We think of this not as a gold standard test, but as one we would add to other tests in making a prediction."

The Harvard Aging Brain Study is funded by the National Institute on Aging. The Northern Manhattan Study is funded by the National Institute of Neurological Disorders and Stroke. Neither Mr. Growdon nor Dr. Devanand had any relevant financial disclosures.

[email protected]

On Twitter @alz_gal

COPENHAGEN – A test that measures how well patients recognize scents was highly correlated with progression from mild cognitive impairment to Alzheimer’s disease as well as neurodegeneration and beta-amyloid deposition in the brain in two separate studies.

Although the test is not ready for use in the clinic, it has the potential to be part of a panel of screening tests to predict the development of Alzheimer’s disease, researchers said at a press briefing during the Alzheimer’s Association International Conference 2014.

© Siri Stafford/Thinkstock

Timely detection of asymptomatic patients is currently lacking, said Dr. David S. Knopman, who moderated the session.

"Our principal clinical tools, including PET and MRI imaging, are excellent, but they are of little value for detecting patients in the preclinical stage of the disease," said Dr. Knopman, professor of neurology at the Mayo Clinic, Rochester, Minn. "These tests, on the other hand, are much simpler, less expensive and invasive, and would be feasible to use in the field, as opposed to only in a large research center."

The studies used the 40-item University of Pennsylvania Smell Identification Test (UPSIT), a scratch-and-sniff test that measures anosmia of mild, moderate, or severe levels, and costs about $25. For patients with Alzheimer’s disease, the test is a measure of memory, revealing an inability to recall once-familiar scent associations.

In one study, Matthew Growdon, a fourth-year medical student at Harvard University, Boston, and his colleagues found a significant relationship between olfactory impairment and pathologic markers of Alzheimer’s disease. The study involved 212 participants of the ongoing Harvard Aging Brain Study, which seeks to identify structural brain changes associated with memory impairment in aging. Participants were cognitively and physically healthy at baseline.

The investigators administered the UPSIT to all subjects, who also underwent a full evaluation to detect signs and symptoms of Alzheimer’s disease. The evaluation included cognitive testing, structural brain scanning, and amyloid imaging, as well as genetic testing and obtaining blood and spinal fluid biomarkers.

A linear regression model evaluated associations between the UPSIT and amyloid burden, hippocampal size, and thinning of the entorhinal cortex. A separate model looked at associations between UPSIT scores and memory test results.

A total of 100 participants were high performers, scoring in the upper 75th percentile of both the UPSIT and the memory tests. The remaining 112 were considered low performers. Of these, 59 scored in the lower 25th percentile of the UPSIT, but in the upper 25th percentile of memory. Nineteen scored in the upper 75th percentile of the UPSIT but the lower 25th percentile of memory, and 34 in the lower 25th percentile of both the UPSIT and memory.

The investigators found a linear correlation between poor UPSIT performance and both lower hippocampal volume on MRI and higher amyloid burden based on Pittsburgh compound B PET imaging. There was a marginal association between poorer UPSIT scores and entorhinal cortex thinning, Mr. Growdon noted.

The associations may indicate that Alzheimer’s pathology affects neurons in the olfactory bulb as well as other brain regions, said Mr. Growdon. "We seem to be looking at neuronal death in all these regions. And what’s really interesting is that this could be the basis of a very simple, low-cost screening tool for a clinically normal, asymptomatic older population. I envision it as something that could flag those at risk of developing symptoms or as a gateway to more expensive or invasive testing.

"It’s not ready for prime-time, though. This is a snapshot of a single moment in time. We would need longitudinal studies before it could be incorporated into care – maybe as part of a panel of screening tests," he said.

Dr. Davangere Devanand presented a second, unrelated study in which he and his colleagues measured the association between olfactory identification impairment and progression from mild cognitive impairment to Alzheimer’s dementia.

The investigation followed 757 participants of the Northern Manhattan Study, a multiethnic community sample in New York that has been used in large part to examine stroke risk factors. The participants initially took the UPSIT during 2004-2006, followed by additional testing during 2006-2008 and 2008-2010.

A total of 109 transitioned from normal cognition to mild cognitive impairment, and then 101 progressed to Alzheimer’s disease.

A low score on the UPSIT test significantly predicted the development of Alzheimer’s with a specificity of 65%. For each one-point decline in UPSIT score, the risk of developing Alzheimer’s increased by 5%.

The specificity of a low score on the UPSIT improved significantly to 77% when combined with the Selective Reminding Test immediate recall subscore. Even alone, the olfactory test was a better predictor of Alzheimer’s than was the memory test, said Dr. Devanand, director of the division of geriatric psychiatry and professor of psychiatry and neurology at Columbia University, New York.

Dr. Devanand said this test would also require further study before it could be incorporated into clinical practice. "We think of this not as a gold standard test, but as one we would add to other tests in making a prediction."

The Harvard Aging Brain Study is funded by the National Institute on Aging. The Northern Manhattan Study is funded by the National Institute of Neurological Disorders and Stroke. Neither Mr. Growdon nor Dr. Devanand had any relevant financial disclosures.

[email protected]

On Twitter @alz_gal

Testicular germ cell tumors are on the rise among Hispanic adolescents and young men, a new study has shown.

From 1992 to 2000, the incidence among Hispanic whites increased 58% – significantly more than the 7% seen in the non-Hispanic white population, according to Franklin L. Chien.

The report was published in the July 14 issue of Cancer.

For the Hispanic males, this translated to an absolute increase of 4 cases/100,000 per year; the absolute increase among non-Hispanic whites was 0.81 cases/100,000 per year, wrote Mr. Chien of Seattle Children’s Hospital, Washington, and his coauthors (Cancer 2014 July 14 [doi:10.1002/cncr.28684]).

The authors extracted their data from the U.S. Surveillance, Epidemiology, and End Results (SEER) database. During 1992-2010, there were 18,545 first diagnoses of testicular germ cell tumors (TGCT) in white males aged 15-39 years. Of these, 3,488 were Hispanic whites and 15,057, non-Hispanic whites.

While TGCT is still significantly more common among non-Hispanic whites, that incidence plateaued over the 19-year study period, with an absolute change of about 1%. In contrast, the annual change for Hispanic males was 3.6 %. This increase affected every 5-year age group from 15 to 39 years, and was present for both seminoma and nonseminoma subtypes.

An analysis of a shorter time span (2000-2010) had essentially the same findings: an annual change of 0.24% for non-Hispanic whites vs. 3.8% for Hispanic whites.

The reasons behind the increase are unclear, the researchers noted. It could be due in part to a more explicit classification of "Hispanic" in the census, but if that were the case, a corresponding rise in other cancers should also have been obvious, they wrote.

TGCT has been linked to environmental factors, including exposure to polyvinylchloride, pesticides, and agricultural work. Marijuana also has been implicated. The authors noted that, compared with blacks and non-Hispanic whites, Hispanic whites are the most likely to use the drug (50% of Hispanic teens compared with 40% of black and 35% of non-Hispanic white teens).

However, "because marijuana use has increased among both Hispanic and non-Hispanic whites, and because the incidence of both seminoma and nonseminoma TGCT rose ... marijuana use alone does not adequately explain the observed increase ..."

The study was funded by the Seattle Children’s Guild Association Teen Cancer Grant. None of the authors had any financial disclosures.

[email protected]

Testicular germ cell tumors are on the rise among Hispanic adolescents and young men, a new study has shown.

From 1992 to 2000, the incidence among Hispanic whites increased 58% – significantly more than the 7% seen in the non-Hispanic white population, according to Franklin L. Chien.

The report was published in the July 14 issue of Cancer.

For the Hispanic males, this translated to an absolute increase of 4 cases/100,000 per year; the absolute increase among non-Hispanic whites was 0.81 cases/100,000 per year, wrote Mr. Chien of Seattle Children’s Hospital, Washington, and his coauthors (Cancer 2014 July 14 [doi:10.1002/cncr.28684]).

The authors extracted their data from the U.S. Surveillance, Epidemiology, and End Results (SEER) database. During 1992-2010, there were 18,545 first diagnoses of testicular germ cell tumors (TGCT) in white males aged 15-39 years. Of these, 3,488 were Hispanic whites and 15,057, non-Hispanic whites.

While TGCT is still significantly more common among non-Hispanic whites, that incidence plateaued over the 19-year study period, with an absolute change of about 1%. In contrast, the annual change for Hispanic males was 3.6 %. This increase affected every 5-year age group from 15 to 39 years, and was present for both seminoma and nonseminoma subtypes.

An analysis of a shorter time span (2000-2010) had essentially the same findings: an annual change of 0.24% for non-Hispanic whites vs. 3.8% for Hispanic whites.

The reasons behind the increase are unclear, the researchers noted. It could be due in part to a more explicit classification of "Hispanic" in the census, but if that were the case, a corresponding rise in other cancers should also have been obvious, they wrote.

TGCT has been linked to environmental factors, including exposure to polyvinylchloride, pesticides, and agricultural work. Marijuana also has been implicated. The authors noted that, compared with blacks and non-Hispanic whites, Hispanic whites are the most likely to use the drug (50% of Hispanic teens compared with 40% of black and 35% of non-Hispanic white teens).

However, "because marijuana use has increased among both Hispanic and non-Hispanic whites, and because the incidence of both seminoma and nonseminoma TGCT rose ... marijuana use alone does not adequately explain the observed increase ..."

The study was funded by the Seattle Children’s Guild Association Teen Cancer Grant. None of the authors had any financial disclosures.

[email protected]

Testicular germ cell tumors are on the rise among Hispanic adolescents and young men, a new study has shown.

From 1992 to 2000, the incidence among Hispanic whites increased 58% – significantly more than the 7% seen in the non-Hispanic white population, according to Franklin L. Chien.

The report was published in the July 14 issue of Cancer.

For the Hispanic males, this translated to an absolute increase of 4 cases/100,000 per year; the absolute increase among non-Hispanic whites was 0.81 cases/100,000 per year, wrote Mr. Chien of Seattle Children’s Hospital, Washington, and his coauthors (Cancer 2014 July 14 [doi:10.1002/cncr.28684]).

The authors extracted their data from the U.S. Surveillance, Epidemiology, and End Results (SEER) database. During 1992-2010, there were 18,545 first diagnoses of testicular germ cell tumors (TGCT) in white males aged 15-39 years. Of these, 3,488 were Hispanic whites and 15,057, non-Hispanic whites.

While TGCT is still significantly more common among non-Hispanic whites, that incidence plateaued over the 19-year study period, with an absolute change of about 1%. In contrast, the annual change for Hispanic males was 3.6 %. This increase affected every 5-year age group from 15 to 39 years, and was present for both seminoma and nonseminoma subtypes.

An analysis of a shorter time span (2000-2010) had essentially the same findings: an annual change of 0.24% for non-Hispanic whites vs. 3.8% for Hispanic whites.

The reasons behind the increase are unclear, the researchers noted. It could be due in part to a more explicit classification of "Hispanic" in the census, but if that were the case, a corresponding rise in other cancers should also have been obvious, they wrote.

TGCT has been linked to environmental factors, including exposure to polyvinylchloride, pesticides, and agricultural work. Marijuana also has been implicated. The authors noted that, compared with blacks and non-Hispanic whites, Hispanic whites are the most likely to use the drug (50% of Hispanic teens compared with 40% of black and 35% of non-Hispanic white teens).

However, "because marijuana use has increased among both Hispanic and non-Hispanic whites, and because the incidence of both seminoma and nonseminoma TGCT rose ... marijuana use alone does not adequately explain the observed increase ..."

The study was funded by the Seattle Children’s Guild Association Teen Cancer Grant. None of the authors had any financial disclosures.

[email protected]

PARIS – Treatment with rituximab in patients with refractory lupus nephritis was associated with significant long-term improvement in symptoms, histology, and laboratory markers in a prospective study.

Over a median follow-up period of 18 months (interquartile range, 12-36 months), the drug normalized proteinuria and was associated with a median reduction in glucocorticoid use of 28 mg/day, according to Dr. Maria Tsanyan of the Nasonova Research Institute of Rheumatology, Moscow.

She and her colleagues followed 60 patients with refractory lupus nephritis who had a median age of 26 years and median disease duration of 37.5 months. At baseline, the patients’ median glomerular filtration rate was 46 mL/min, and their median amount of proteinuria was 1.83 g/day. A total of 14 patients (23%) had nephrotic syndrome.

All patients had failed prior therapy. These treatments included high-dose glucocorticoids (45%), pulsed high-dose glucocorticoid and cyclophosphamide (90%), mycophenolate mofetil (17%), azathioprine (7%), hydroxychloroquine (17%), and cyclosporine A (8%).

Treatment with rituximab varied according to clinical status and response. The initial doses were 1,000 mg in 25 patients and 2,000 mg in 30 patients. Five patients did not receive a full initial course of rituximab because of the development of end-stage renal disease, including four who received only 500 mg and one who received 1,500 mg.

Most (37) required more than one course: 21 needed two courses, 11 needed three, 4 needed four courses, and 1 received five courses of the drug.

In response to an audience member’s question about the basis on which the investigators decided to re-treat patients with rituximab, Dr. Tsanyan said that they tried to achieve complete responses in patients with disease exacerbation or partial response at 6 months or 12 months after the initial dose.

Based on the Systemic Lupus Erythematosus International Collaborating Clinics renal activity/response exercise criteria, 58% had a complete response, 22% had a partial response, 12% were nonresponders, and 8% died of acute renal failure. Overall, 28% of patients had an exacerbation of disease during treatment.

There was no difference in response between patients who received 1,000 mg and 2,000 mg rituximab, she said at the annual European Congress of Rheumatology.

By 6 months of treatment, the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score had decreased from 20 to 4. This improvement held at 12 months. By 42 months, the median score had dropped to 2. By SLEDAI-2K index, 50% were considered to be complete responders, 30% partial responders, and 12% nonresponders.

Antibodies to double-stranded DNA fell from a mean of 67.7 U/mL at baseline to 34.5 U/mL at 42 months. Daily glucocorticoid use dropped from 35 mg to 7.5 mg.

C3 and C4 complement components also improved. C3 rose from 0.7 to 0.98 g/L, and C4 from 0.1 g/L to 0.24 g/L. Daily proteinuria fell from 1.6 g/day to 0.01 g/day and serum total protein rose from 59 g/L to 72 g/L.

Sixteen patients had renal biopsies both at baseline and at the end of their follow-up period. Of 14 patients who had World Health Organization class IV nephritis at baseline, 5 were unchanged, 3 moved to class III, 5 to class II, and 1 to class I. Two class III patients improved to class I.

There were 13 adverse events, all of which occurred during the first 3 months of rituximab therapy. These included pneumonia (4), aspergillosis (1), bronchitis (1), cystitis (2), shingles (3), furunculosis (1) and pityriasis versicolor (1).

Dr. Tsanyan did not have any financial disclosures.

[email protected]

PARIS – Treatment with rituximab in patients with refractory lupus nephritis was associated with significant long-term improvement in symptoms, histology, and laboratory markers in a prospective study.

Over a median follow-up period of 18 months (interquartile range, 12-36 months), the drug normalized proteinuria and was associated with a median reduction in glucocorticoid use of 28 mg/day, according to Dr. Maria Tsanyan of the Nasonova Research Institute of Rheumatology, Moscow.

She and her colleagues followed 60 patients with refractory lupus nephritis who had a median age of 26 years and median disease duration of 37.5 months. At baseline, the patients’ median glomerular filtration rate was 46 mL/min, and their median amount of proteinuria was 1.83 g/day. A total of 14 patients (23%) had nephrotic syndrome.

All patients had failed prior therapy. These treatments included high-dose glucocorticoids (45%), pulsed high-dose glucocorticoid and cyclophosphamide (90%), mycophenolate mofetil (17%), azathioprine (7%), hydroxychloroquine (17%), and cyclosporine A (8%).

Treatment with rituximab varied according to clinical status and response. The initial doses were 1,000 mg in 25 patients and 2,000 mg in 30 patients. Five patients did not receive a full initial course of rituximab because of the development of end-stage renal disease, including four who received only 500 mg and one who received 1,500 mg.

Most (37) required more than one course: 21 needed two courses, 11 needed three, 4 needed four courses, and 1 received five courses of the drug.

In response to an audience member’s question about the basis on which the investigators decided to re-treat patients with rituximab, Dr. Tsanyan said that they tried to achieve complete responses in patients with disease exacerbation or partial response at 6 months or 12 months after the initial dose.

Based on the Systemic Lupus Erythematosus International Collaborating Clinics renal activity/response exercise criteria, 58% had a complete response, 22% had a partial response, 12% were nonresponders, and 8% died of acute renal failure. Overall, 28% of patients had an exacerbation of disease during treatment.

There was no difference in response between patients who received 1,000 mg and 2,000 mg rituximab, she said at the annual European Congress of Rheumatology.

By 6 months of treatment, the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score had decreased from 20 to 4. This improvement held at 12 months. By 42 months, the median score had dropped to 2. By SLEDAI-2K index, 50% were considered to be complete responders, 30% partial responders, and 12% nonresponders.

Antibodies to double-stranded DNA fell from a mean of 67.7 U/mL at baseline to 34.5 U/mL at 42 months. Daily glucocorticoid use dropped from 35 mg to 7.5 mg.

C3 and C4 complement components also improved. C3 rose from 0.7 to 0.98 g/L, and C4 from 0.1 g/L to 0.24 g/L. Daily proteinuria fell from 1.6 g/day to 0.01 g/day and serum total protein rose from 59 g/L to 72 g/L.

Sixteen patients had renal biopsies both at baseline and at the end of their follow-up period. Of 14 patients who had World Health Organization class IV nephritis at baseline, 5 were unchanged, 3 moved to class III, 5 to class II, and 1 to class I. Two class III patients improved to class I.

There were 13 adverse events, all of which occurred during the first 3 months of rituximab therapy. These included pneumonia (4), aspergillosis (1), bronchitis (1), cystitis (2), shingles (3), furunculosis (1) and pityriasis versicolor (1).

Dr. Tsanyan did not have any financial disclosures.

[email protected]

PARIS – Treatment with rituximab in patients with refractory lupus nephritis was associated with significant long-term improvement in symptoms, histology, and laboratory markers in a prospective study.

Over a median follow-up period of 18 months (interquartile range, 12-36 months), the drug normalized proteinuria and was associated with a median reduction in glucocorticoid use of 28 mg/day, according to Dr. Maria Tsanyan of the Nasonova Research Institute of Rheumatology, Moscow.

She and her colleagues followed 60 patients with refractory lupus nephritis who had a median age of 26 years and median disease duration of 37.5 months. At baseline, the patients’ median glomerular filtration rate was 46 mL/min, and their median amount of proteinuria was 1.83 g/day. A total of 14 patients (23%) had nephrotic syndrome.

All patients had failed prior therapy. These treatments included high-dose glucocorticoids (45%), pulsed high-dose glucocorticoid and cyclophosphamide (90%), mycophenolate mofetil (17%), azathioprine (7%), hydroxychloroquine (17%), and cyclosporine A (8%).

Treatment with rituximab varied according to clinical status and response. The initial doses were 1,000 mg in 25 patients and 2,000 mg in 30 patients. Five patients did not receive a full initial course of rituximab because of the development of end-stage renal disease, including four who received only 500 mg and one who received 1,500 mg.

Most (37) required more than one course: 21 needed two courses, 11 needed three, 4 needed four courses, and 1 received five courses of the drug.

In response to an audience member’s question about the basis on which the investigators decided to re-treat patients with rituximab, Dr. Tsanyan said that they tried to achieve complete responses in patients with disease exacerbation or partial response at 6 months or 12 months after the initial dose.

Based on the Systemic Lupus Erythematosus International Collaborating Clinics renal activity/response exercise criteria, 58% had a complete response, 22% had a partial response, 12% were nonresponders, and 8% died of acute renal failure. Overall, 28% of patients had an exacerbation of disease during treatment.

There was no difference in response between patients who received 1,000 mg and 2,000 mg rituximab, she said at the annual European Congress of Rheumatology.

By 6 months of treatment, the median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score had decreased from 20 to 4. This improvement held at 12 months. By 42 months, the median score had dropped to 2. By SLEDAI-2K index, 50% were considered to be complete responders, 30% partial responders, and 12% nonresponders.

Antibodies to double-stranded DNA fell from a mean of 67.7 U/mL at baseline to 34.5 U/mL at 42 months. Daily glucocorticoid use dropped from 35 mg to 7.5 mg.

C3 and C4 complement components also improved. C3 rose from 0.7 to 0.98 g/L, and C4 from 0.1 g/L to 0.24 g/L. Daily proteinuria fell from 1.6 g/day to 0.01 g/day and serum total protein rose from 59 g/L to 72 g/L.

Sixteen patients had renal biopsies both at baseline and at the end of their follow-up period. Of 14 patients who had World Health Organization class IV nephritis at baseline, 5 were unchanged, 3 moved to class III, 5 to class II, and 1 to class I. Two class III patients improved to class I.

There were 13 adverse events, all of which occurred during the first 3 months of rituximab therapy. These included pneumonia (4), aspergillosis (1), bronchitis (1), cystitis (2), shingles (3), furunculosis (1) and pityriasis versicolor (1).

Dr. Tsanyan did not have any financial disclosures.

[email protected]

PARIS – A randomized trial of two doses of atacicept for systemic lupus erythematosus was interrupted after two deaths occurred in patients taking 150 mg of the drug.

However, since a post hoc analysis concluded that the 150-mg dose was more effective at reducing flares than was the 75-mg dose, research on it continues, Dr. Caroline Gordon said at the annual European Congress of Rheumatology.

Additionally, said Dr. Gordon, professor of rheumatology at the University of Birmingham, England, the 150-mg dose was significantly more effective than was the 75-mg dose or placebo at reducing mucocutaneous and musculoskeletal flares (9% vs. 18%).

"This finding, and the suggestion that atacicept may have a steroid-sparing effect, allows for assessing its safety and efficacy further," she said.

EMD Serono, a subsidiary of Merck, is now recruiting for a 24-week trial comparing the 75- and 150-mg doses in patients with systemic lupus erythematosus (SLE).

Atacicept is an investigational, fully human recombinant fusion protein that inhibits B-lymphocyte stimulator (BLyS) and the A proliferation-inducing ligand (APRIL). Both proteins stimulate B-cell production and are elevated in patients with lupus.

At the congress, Dr. Gordon reported the results of the APRIL-SLE study, which randomized 461 patients to atacicept at either dose or placebo. Its primary endpoint was the rate of new flares in patients with lupus. Secondary endpoints included changes in disease activity scores, overall safety, biomarkers, and pharmacodynamics. The full results of the study were published after the congress (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-205067]).

Patients had to achieve stable condition before being randomized. After screening, they were assigned to a 10-week corticosteroid taper. If they had improved to a score of C or D on the British Isles Assessment Group (BILAG) scale, they were randomized. After the 52-week treatment period, there was a 24-week safety observation period.

Most patients in the placebo and 75-mg groups completed the study (70%). In the 150-mg arm, 43% completed the trial. After the two deaths, 38% patients in the 150 mg-arm stopped treatment. Both patients died of pneumonia complicated by pulmonary hemorrhage.

One of these was a 22-year-old man from the Philippines on week 42 of treatment, who had complicating comorbidities of systemic sclerosis and may have had leptospirosis as well, Dr. Gordon said. "There may have also been some delays in getting him treated, although we are not sure of that."

The other was a 30-year-old woman on treatment week 22. She developed a pneumococcal pneumonia "and deteriorated rapidly," Dr. Gordon said.

There were no withdrawals because of infection or any other adverse events in any of the treatment groups.

The patients had a mean age of 39 years, and most were women (93%). The mean disease severity by BILAG score was A (severe) in 31% and B (moderate) in the remainder.

In the primary intent-to-treat analysis, there was no significant difference between placebo and 75 mg in flare rate. The 150-mg dose was associated with significantly fewer flares than was placebo (40% vs. 55%), but the difference between it and the lower dose was not statistically significant. Both doses prolonged the time to first flare significantly more than placebo.

The investigators also conducted a post hoc, potential completer analysis to examine the effect in all patients who had completed the entire 52 weeks of treatment. Atacicept 75 mg was not significantly better than placebo, but the 150-mg dose was, reducing the odds of a flare by 51% (flare rate 43% vs. 60%) – a finding similar to the intent-to-treat analysis.

The largest portion of flares (about 23%) was in the mucocutaneous and musculoskeletal systems. The 150-mg dose halved the occurrence of these flares relative to placebo.

The study was not powered to detect flare severity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). However, another post hoc analysis concluded that, compared with placebo, the 150-mg dose reduced the chance of a severe flare by 55% on SLEDAI scoring.

The study was sponsored by EMD Serono, a subsidiary of Merck. Dr. Gordon disclosed that she received personal remuneration from Merck Serono during the study. The three coauthors were Merck employees.

[email protected]

On Twitter @alz_gal

PARIS – A randomized trial of two doses of atacicept for systemic lupus erythematosus was interrupted after two deaths occurred in patients taking 150 mg of the drug.

However, since a post hoc analysis concluded that the 150-mg dose was more effective at reducing flares than was the 75-mg dose, research on it continues, Dr. Caroline Gordon said at the annual European Congress of Rheumatology.

Additionally, said Dr. Gordon, professor of rheumatology at the University of Birmingham, England, the 150-mg dose was significantly more effective than was the 75-mg dose or placebo at reducing mucocutaneous and musculoskeletal flares (9% vs. 18%).

"This finding, and the suggestion that atacicept may have a steroid-sparing effect, allows for assessing its safety and efficacy further," she said.

EMD Serono, a subsidiary of Merck, is now recruiting for a 24-week trial comparing the 75- and 150-mg doses in patients with systemic lupus erythematosus (SLE).

Atacicept is an investigational, fully human recombinant fusion protein that inhibits B-lymphocyte stimulator (BLyS) and the A proliferation-inducing ligand (APRIL). Both proteins stimulate B-cell production and are elevated in patients with lupus.

At the congress, Dr. Gordon reported the results of the APRIL-SLE study, which randomized 461 patients to atacicept at either dose or placebo. Its primary endpoint was the rate of new flares in patients with lupus. Secondary endpoints included changes in disease activity scores, overall safety, biomarkers, and pharmacodynamics. The full results of the study were published after the congress (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-205067]).

Patients had to achieve stable condition before being randomized. After screening, they were assigned to a 10-week corticosteroid taper. If they had improved to a score of C or D on the British Isles Assessment Group (BILAG) scale, they were randomized. After the 52-week treatment period, there was a 24-week safety observation period.

Most patients in the placebo and 75-mg groups completed the study (70%). In the 150-mg arm, 43% completed the trial. After the two deaths, 38% patients in the 150 mg-arm stopped treatment. Both patients died of pneumonia complicated by pulmonary hemorrhage.

One of these was a 22-year-old man from the Philippines on week 42 of treatment, who had complicating comorbidities of systemic sclerosis and may have had leptospirosis as well, Dr. Gordon said. "There may have also been some delays in getting him treated, although we are not sure of that."

The other was a 30-year-old woman on treatment week 22. She developed a pneumococcal pneumonia "and deteriorated rapidly," Dr. Gordon said.

There were no withdrawals because of infection or any other adverse events in any of the treatment groups.

The patients had a mean age of 39 years, and most were women (93%). The mean disease severity by BILAG score was A (severe) in 31% and B (moderate) in the remainder.

In the primary intent-to-treat analysis, there was no significant difference between placebo and 75 mg in flare rate. The 150-mg dose was associated with significantly fewer flares than was placebo (40% vs. 55%), but the difference between it and the lower dose was not statistically significant. Both doses prolonged the time to first flare significantly more than placebo.

The investigators also conducted a post hoc, potential completer analysis to examine the effect in all patients who had completed the entire 52 weeks of treatment. Atacicept 75 mg was not significantly better than placebo, but the 150-mg dose was, reducing the odds of a flare by 51% (flare rate 43% vs. 60%) – a finding similar to the intent-to-treat analysis.

The largest portion of flares (about 23%) was in the mucocutaneous and musculoskeletal systems. The 150-mg dose halved the occurrence of these flares relative to placebo.

The study was not powered to detect flare severity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). However, another post hoc analysis concluded that, compared with placebo, the 150-mg dose reduced the chance of a severe flare by 55% on SLEDAI scoring.

The study was sponsored by EMD Serono, a subsidiary of Merck. Dr. Gordon disclosed that she received personal remuneration from Merck Serono during the study. The three coauthors were Merck employees.

[email protected]

On Twitter @alz_gal

PARIS – A randomized trial of two doses of atacicept for systemic lupus erythematosus was interrupted after two deaths occurred in patients taking 150 mg of the drug.

However, since a post hoc analysis concluded that the 150-mg dose was more effective at reducing flares than was the 75-mg dose, research on it continues, Dr. Caroline Gordon said at the annual European Congress of Rheumatology.

Additionally, said Dr. Gordon, professor of rheumatology at the University of Birmingham, England, the 150-mg dose was significantly more effective than was the 75-mg dose or placebo at reducing mucocutaneous and musculoskeletal flares (9% vs. 18%).

"This finding, and the suggestion that atacicept may have a steroid-sparing effect, allows for assessing its safety and efficacy further," she said.

EMD Serono, a subsidiary of Merck, is now recruiting for a 24-week trial comparing the 75- and 150-mg doses in patients with systemic lupus erythematosus (SLE).

Atacicept is an investigational, fully human recombinant fusion protein that inhibits B-lymphocyte stimulator (BLyS) and the A proliferation-inducing ligand (APRIL). Both proteins stimulate B-cell production and are elevated in patients with lupus.

At the congress, Dr. Gordon reported the results of the APRIL-SLE study, which randomized 461 patients to atacicept at either dose or placebo. Its primary endpoint was the rate of new flares in patients with lupus. Secondary endpoints included changes in disease activity scores, overall safety, biomarkers, and pharmacodynamics. The full results of the study were published after the congress (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-205067]).

Patients had to achieve stable condition before being randomized. After screening, they were assigned to a 10-week corticosteroid taper. If they had improved to a score of C or D on the British Isles Assessment Group (BILAG) scale, they were randomized. After the 52-week treatment period, there was a 24-week safety observation period.

Most patients in the placebo and 75-mg groups completed the study (70%). In the 150-mg arm, 43% completed the trial. After the two deaths, 38% patients in the 150 mg-arm stopped treatment. Both patients died of pneumonia complicated by pulmonary hemorrhage.

One of these was a 22-year-old man from the Philippines on week 42 of treatment, who had complicating comorbidities of systemic sclerosis and may have had leptospirosis as well, Dr. Gordon said. "There may have also been some delays in getting him treated, although we are not sure of that."

The other was a 30-year-old woman on treatment week 22. She developed a pneumococcal pneumonia "and deteriorated rapidly," Dr. Gordon said.

There were no withdrawals because of infection or any other adverse events in any of the treatment groups.

The patients had a mean age of 39 years, and most were women (93%). The mean disease severity by BILAG score was A (severe) in 31% and B (moderate) in the remainder.

In the primary intent-to-treat analysis, there was no significant difference between placebo and 75 mg in flare rate. The 150-mg dose was associated with significantly fewer flares than was placebo (40% vs. 55%), but the difference between it and the lower dose was not statistically significant. Both doses prolonged the time to first flare significantly more than placebo.

The investigators also conducted a post hoc, potential completer analysis to examine the effect in all patients who had completed the entire 52 weeks of treatment. Atacicept 75 mg was not significantly better than placebo, but the 150-mg dose was, reducing the odds of a flare by 51% (flare rate 43% vs. 60%) – a finding similar to the intent-to-treat analysis.

The largest portion of flares (about 23%) was in the mucocutaneous and musculoskeletal systems. The 150-mg dose halved the occurrence of these flares relative to placebo.

The study was not powered to detect flare severity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). However, another post hoc analysis concluded that, compared with placebo, the 150-mg dose reduced the chance of a severe flare by 55% on SLEDAI scoring.

The study was sponsored by EMD Serono, a subsidiary of Merck. Dr. Gordon disclosed that she received personal remuneration from Merck Serono during the study. The three coauthors were Merck employees.

[email protected]

On Twitter @alz_gal

Adults and children who are unvaccinated or not up to date on polio vaccinations should get a booster or complete their series before traveling to countries where poliovirus is now being reported, according to the Centers for Disease Control and Prevention.

Some travelers, regardless of immunization status, may also be required to obtain a booster dose before leaving the infected countries: Afghanistan, Nigeria, and Pakistan – where polio is endemic – and Cameroon, Ethiopia, Equatorial Guinea, Iraq, Israel, Somalia, and Syria, where wild poliovirus is now circulating.

"Travelers working in health care settings, refugee camps, or other humanitarian aid settings in these and neighboring countries might be at particular risk for exposure to wild poliovirus," Dr. Gregory S. Wallace and his colleagues reported in the July 7 issue of the Morbidity and Mortality Weekly Report.

Adults who have completed a routine polio vaccination series are considered to have lifelong immunity, although supporting data for this assumption are currently lacking. Adults who are unvaccinated or incompletely vaccinated, or whose status is unknown, need to have at least one inactivated polio vaccine for short-notice travel, and up to three if travel is at least 8 weeks away, wrote Dr. Wallace, who leads the CDC’s measles/mumps, rubella, and polio team, and his coauthors.

Unvaccinated or incompletely vaccinated infants and children should have an accelerated series before traveling to infected countries. The first dose should be given to infants who are at lest 6 weeks old and both the second and third at least 4 weeks after the previous doses. However, the minimum interval between doses three and four should be at least 6 months (MMWR 2014;63:1-4).

The recommendations should also prevent travel problems that could face unvaccinated or incompletely vaccinated persons who are trying to enter or leave an infected country, Dr. Wallace and his colleagues noted. The World Health Organization may shortly implement vaccination requirements for these countries.

Countries known to be exporting wild poliovirus (Cameroon, Equatorial Guinea, Pakistan, and Syria) should ensure complete vaccination of departing residents and travelers with visits of at least 1 month. The other six infected countries "should encourage polio vaccination boosters among departing residents and long-term travelers," according to the CDC.

This recommendation could change at the end of July when WHO reassesses the polio public health emergency officials called last spring.

To help avoid problems, the CDC recommends that all polio vaccinations be documented on an International Certificate of Vaccination or Prophylaxis (the "yellow card"). Even children who have a complete polio series should receive a booster before they leave an infected country. Adults with documentation of a series may also be required to receive a booster before leaving.

Adults and children who are unvaccinated or not up to date on polio vaccinations should get a booster or complete their series before traveling to countries where poliovirus is now being reported, according to the Centers for Disease Control and Prevention.

Some travelers, regardless of immunization status, may also be required to obtain a booster dose before leaving the infected countries: Afghanistan, Nigeria, and Pakistan – where polio is endemic – and Cameroon, Ethiopia, Equatorial Guinea, Iraq, Israel, Somalia, and Syria, where wild poliovirus is now circulating.

"Travelers working in health care settings, refugee camps, or other humanitarian aid settings in these and neighboring countries might be at particular risk for exposure to wild poliovirus," Dr. Gregory S. Wallace and his colleagues reported in the July 7 issue of the Morbidity and Mortality Weekly Report.

Adults who have completed a routine polio vaccination series are considered to have lifelong immunity, although supporting data for this assumption are currently lacking. Adults who are unvaccinated or incompletely vaccinated, or whose status is unknown, need to have at least one inactivated polio vaccine for short-notice travel, and up to three if travel is at least 8 weeks away, wrote Dr. Wallace, who leads the CDC’s measles/mumps, rubella, and polio team, and his coauthors.

Unvaccinated or incompletely vaccinated infants and children should have an accelerated series before traveling to infected countries. The first dose should be given to infants who are at lest 6 weeks old and both the second and third at least 4 weeks after the previous doses. However, the minimum interval between doses three and four should be at least 6 months (MMWR 2014;63:1-4).

The recommendations should also prevent travel problems that could face unvaccinated or incompletely vaccinated persons who are trying to enter or leave an infected country, Dr. Wallace and his colleagues noted. The World Health Organization may shortly implement vaccination requirements for these countries.

Countries known to be exporting wild poliovirus (Cameroon, Equatorial Guinea, Pakistan, and Syria) should ensure complete vaccination of departing residents and travelers with visits of at least 1 month. The other six infected countries "should encourage polio vaccination boosters among departing residents and long-term travelers," according to the CDC.

This recommendation could change at the end of July when WHO reassesses the polio public health emergency officials called last spring.

To help avoid problems, the CDC recommends that all polio vaccinations be documented on an International Certificate of Vaccination or Prophylaxis (the "yellow card"). Even children who have a complete polio series should receive a booster before they leave an infected country. Adults with documentation of a series may also be required to receive a booster before leaving.

Adults and children who are unvaccinated or not up to date on polio vaccinations should get a booster or complete their series before traveling to countries where poliovirus is now being reported, according to the Centers for Disease Control and Prevention.

Some travelers, regardless of immunization status, may also be required to obtain a booster dose before leaving the infected countries: Afghanistan, Nigeria, and Pakistan – where polio is endemic – and Cameroon, Ethiopia, Equatorial Guinea, Iraq, Israel, Somalia, and Syria, where wild poliovirus is now circulating.

"Travelers working in health care settings, refugee camps, or other humanitarian aid settings in these and neighboring countries might be at particular risk for exposure to wild poliovirus," Dr. Gregory S. Wallace and his colleagues reported in the July 7 issue of the Morbidity and Mortality Weekly Report.

Adults who have completed a routine polio vaccination series are considered to have lifelong immunity, although supporting data for this assumption are currently lacking. Adults who are unvaccinated or incompletely vaccinated, or whose status is unknown, need to have at least one inactivated polio vaccine for short-notice travel, and up to three if travel is at least 8 weeks away, wrote Dr. Wallace, who leads the CDC’s measles/mumps, rubella, and polio team, and his coauthors.

Unvaccinated or incompletely vaccinated infants and children should have an accelerated series before traveling to infected countries. The first dose should be given to infants who are at lest 6 weeks old and both the second and third at least 4 weeks after the previous doses. However, the minimum interval between doses three and four should be at least 6 months (MMWR 2014;63:1-4).

The recommendations should also prevent travel problems that could face unvaccinated or incompletely vaccinated persons who are trying to enter or leave an infected country, Dr. Wallace and his colleagues noted. The World Health Organization may shortly implement vaccination requirements for these countries.

Countries known to be exporting wild poliovirus (Cameroon, Equatorial Guinea, Pakistan, and Syria) should ensure complete vaccination of departing residents and travelers with visits of at least 1 month. The other six infected countries "should encourage polio vaccination boosters among departing residents and long-term travelers," according to the CDC.

This recommendation could change at the end of July when WHO reassesses the polio public health emergency officials called last spring.

To help avoid problems, the CDC recommends that all polio vaccinations be documented on an International Certificate of Vaccination or Prophylaxis (the "yellow card"). Even children who have a complete polio series should receive a booster before they leave an infected country. Adults with documentation of a series may also be required to receive a booster before leaving.

Adults and children who are unvaccinated or not up to date on polio vaccinations should get a booster or complete their series before traveling to countries where poliovirus is now being reported, according to the Centers for Disease Control and Prevention.

Some travelers, regardless of immunization status, may also be required to obtain a booster dose before leaving the infected countries: Afghanistan, Nigeria, and Pakistan – where polio is endemic – and Cameroon, Ethiopia, Equatorial Guinea, Iraq, Israel, Somalia, and Syria, where wild poliovirus is now circulating.

© BananaStock /Thinkstockphotos.com

"Travelers working in health care settings, refugee camps, or other humanitarian aid settings in these and neighboring countries might be at particular risk for exposure to wild poliovirus," Dr. Gregory S. Wallace and his colleagues reported in the July 7 issue of the Morbidity and Mortality Weekly Report.

Adults who have completed a routine polio vaccination series are considered to have lifelong immunity, although supporting data for this assumption are currently lacking. Adults who are unvaccinated or incompletely vaccinated, or whose status is unknown, need to have at least one inactivated polio vaccine for short-notice travel, and up to three if travel is at least 8 weeks away, wrote Dr. Wallace, who leads the CDC’s measles/mumps, rubella, and polio team, and his coauthors.

Unvaccinated or incompletely vaccinated infants and children should have an accelerated series before traveling to infected countries. The first dose should be given to infants who are at lest 6 weeks old and both the second and third at least 4 weeks after the previous doses. However, the minimum interval between doses three and four should be at least 6 months (MMWR 2014;63:1-4).

The recommendations should also prevent travel problems that could face unvaccinated or incompletely vaccinated persons who are trying to enter or leave an infected country, Dr. Wallace and his colleagues noted. The World Health Organization may shortly implement vaccination requirements for these countries.

Countries known to be exporting wild poliovirus (Cameroon, Equatorial Guinea, Pakistan, and Syria) should ensure complete vaccination of departing residents and travelers with visits of at least 1 month. The other six infected countries "should encourage polio vaccination boosters among departing residents and long-term travelers," according to the CDC.

This recommendation could change at the end of July when WHO reassesses the polio public health emergency officials called last spring.

To help avoid problems, the CDC recommends that all polio vaccinations be documented on an International Certificate of Vaccination or Prophylaxis (the "yellow card"). Even children who have a complete polio series should receive a booster before they leave an infected country. Adults with documentation of a series may also be required to receive a booster before leaving.

[email protected]

Adults and children who are unvaccinated or not up to date on polio vaccinations should get a booster or complete their series before traveling to countries where poliovirus is now being reported, according to the Centers for Disease Control and Prevention.

Some travelers, regardless of immunization status, may also be required to obtain a booster dose before leaving the infected countries: Afghanistan, Nigeria, and Pakistan – where polio is endemic – and Cameroon, Ethiopia, Equatorial Guinea, Iraq, Israel, Somalia, and Syria, where wild poliovirus is now circulating.

© BananaStock /Thinkstockphotos.com

"Travelers working in health care settings, refugee camps, or other humanitarian aid settings in these and neighboring countries might be at particular risk for exposure to wild poliovirus," Dr. Gregory S. Wallace and his colleagues reported in the July 7 issue of the Morbidity and Mortality Weekly Report.

Adults who have completed a routine polio vaccination series are considered to have lifelong immunity, although supporting data for this assumption are currently lacking. Adults who are unvaccinated or incompletely vaccinated, or whose status is unknown, need to have at least one inactivated polio vaccine for short-notice travel, and up to three if travel is at least 8 weeks away, wrote Dr. Wallace, who leads the CDC’s measles/mumps, rubella, and polio team, and his coauthors.

Unvaccinated or incompletely vaccinated infants and children should have an accelerated series before traveling to infected countries. The first dose should be given to infants who are at lest 6 weeks old and both the second and third at least 4 weeks after the previous doses. However, the minimum interval between doses three and four should be at least 6 months (MMWR 2014;63:1-4).

The recommendations should also prevent travel problems that could face unvaccinated or incompletely vaccinated persons who are trying to enter or leave an infected country, Dr. Wallace and his colleagues noted. The World Health Organization may shortly implement vaccination requirements for these countries.

Countries known to be exporting wild poliovirus (Cameroon, Equatorial Guinea, Pakistan, and Syria) should ensure complete vaccination of departing residents and travelers with visits of at least 1 month. The other six infected countries "should encourage polio vaccination boosters among departing residents and long-term travelers," according to the CDC.

This recommendation could change at the end of July when WHO reassesses the polio public health emergency officials called last spring.

To help avoid problems, the CDC recommends that all polio vaccinations be documented on an International Certificate of Vaccination or Prophylaxis (the "yellow card"). Even children who have a complete polio series should receive a booster before they leave an infected country. Adults with documentation of a series may also be required to receive a booster before leaving.

[email protected]

Adults and children who are unvaccinated or not up to date on polio vaccinations should get a booster or complete their series before traveling to countries where poliovirus is now being reported, according to the Centers for Disease Control and Prevention.

Some travelers, regardless of immunization status, may also be required to obtain a booster dose before leaving the infected countries: Afghanistan, Nigeria, and Pakistan – where polio is endemic – and Cameroon, Ethiopia, Equatorial Guinea, Iraq, Israel, Somalia, and Syria, where wild poliovirus is now circulating.

© BananaStock /Thinkstockphotos.com

"Travelers working in health care settings, refugee camps, or other humanitarian aid settings in these and neighboring countries might be at particular risk for exposure to wild poliovirus," Dr. Gregory S. Wallace and his colleagues reported in the July 7 issue of the Morbidity and Mortality Weekly Report.

Adults who have completed a routine polio vaccination series are considered to have lifelong immunity, although supporting data for this assumption are currently lacking. Adults who are unvaccinated or incompletely vaccinated, or whose status is unknown, need to have at least one inactivated polio vaccine for short-notice travel, and up to three if travel is at least 8 weeks away, wrote Dr. Wallace, who leads the CDC’s measles/mumps, rubella, and polio team, and his coauthors.

Unvaccinated or incompletely vaccinated infants and children should have an accelerated series before traveling to infected countries. The first dose should be given to infants who are at lest 6 weeks old and both the second and third at least 4 weeks after the previous doses. However, the minimum interval between doses three and four should be at least 6 months (MMWR 2014;63:1-4).

The recommendations should also prevent travel problems that could face unvaccinated or incompletely vaccinated persons who are trying to enter or leave an infected country, Dr. Wallace and his colleagues noted. The World Health Organization may shortly implement vaccination requirements for these countries.

Countries known to be exporting wild poliovirus (Cameroon, Equatorial Guinea, Pakistan, and Syria) should ensure complete vaccination of departing residents and travelers with visits of at least 1 month. The other six infected countries "should encourage polio vaccination boosters among departing residents and long-term travelers," according to the CDC.

This recommendation could change at the end of July when WHO reassesses the polio public health emergency officials called last spring.

To help avoid problems, the CDC recommends that all polio vaccinations be documented on an International Certificate of Vaccination or Prophylaxis (the "yellow card"). Even children who have a complete polio series should receive a booster before they leave an infected country. Adults with documentation of a series may also be required to receive a booster before leaving.

[email protected]

PARIS – The investigational interleukin-6 blocker sirukumab provided no benefit to patients with lupus nephritis but put them at a very high risk of developing a serious infection in a small, randomized, placebo-controlled trial.

Based on the study results, the study sponsor, Janssen, has shut down its program for the lupus nephritis indication, Dr. Ronald van Vollenhoven said at the annual European Congress of Rheumatology.

"While a few patients did experience a reduction in proteinuria, we had an unacceptably high rate of adverse events," said Dr. van Vollenhoven, chief of the Unit for Clinical Therapy Research, Inflammatory Diseases, at the Karolinska Institute, Stockholm. "Based on these findings, we will not be advancing any further investigation of sirukumab for patients with active lupus nephritis."

The company continues to develop the drug for rheumatoid arthritis.

In the trial, 21 patients received intravenous sirukumab 10 mg/kg once every 4 weeks for 24 weeks, and 4 received placebo. During the trial and a 16-week safety observation follow-up period, 48% of those who took the investigational IL-6 blocker developed a serious adverse event, including infections serious enough to require hospital admission.

While not specifying the infections, which occurred in 10 patients, Dr. van Vollenhoven noted that five patients taking the drug discontinued it because of adverse events, which included Haemophilus influenzae pneumonia, elevated liver enzymes, anaphylactic reaction after the first dose, worsening nephritis, and severe neutropenia.

Overall, 19 patients completed the study. In addition to the five who quit because of adverse events, one additional patient withdrew voluntarily. All had active lupus nephritis of about 50 months’ duration, with a mean daily proteinuria of more than 2 g; about a third of the group had nephrotic proteinuria. The mean Systemic Lupus Erythematosus Disease Activity Index 2000 was about 16. All were taking concomitant mycophenolate mofetil or azathioprine.

At the end of the treatment period, there was no significant between-group difference in proteinuria, Dr. van Vollenhoven said. Four of those in the active group experienced at least a 50% reduction in proteinuria over baseline, while none of those in the placebo group experienced this change. However, this difference was not statistically significant. There were no significant changes in the patient or physical global assessment for either group.

Serious adverse events occurred in 48% of those taking the drug, including serious infections (30%) as well as renal/urinary (19%), blood (9.5%), and gastrointestinal (9.5%) events. None occurred in the placebo group.

Among patients in the sirukumab group, there was one grade 4 lymphocytopenia, one grade 4 neutropenia, and two grade 3 neutropenias. One patient had a grade 2 liver enzyme elevation.

Dr. van Vollenhoven was on the study steering committee and is a consultant and speaker for Janssen, as well as other drug manufacturers. Four coauthors are employees of Janssen.

[email protected]

PARIS – The investigational interleukin-6 blocker sirukumab provided no benefit to patients with lupus nephritis but put them at a very high risk of developing a serious infection in a small, randomized, placebo-controlled trial.

Based on the study results, the study sponsor, Janssen, has shut down its program for the lupus nephritis indication, Dr. Ronald van Vollenhoven said at the annual European Congress of Rheumatology.

"While a few patients did experience a reduction in proteinuria, we had an unacceptably high rate of adverse events," said Dr. van Vollenhoven, chief of the Unit for Clinical Therapy Research, Inflammatory Diseases, at the Karolinska Institute, Stockholm. "Based on these findings, we will not be advancing any further investigation of sirukumab for patients with active lupus nephritis."

The company continues to develop the drug for rheumatoid arthritis.

In the trial, 21 patients received intravenous sirukumab 10 mg/kg once every 4 weeks for 24 weeks, and 4 received placebo. During the trial and a 16-week safety observation follow-up period, 48% of those who took the investigational IL-6 blocker developed a serious adverse event, including infections serious enough to require hospital admission.

While not specifying the infections, which occurred in 10 patients, Dr. van Vollenhoven noted that five patients taking the drug discontinued it because of adverse events, which included Haemophilus influenzae pneumonia, elevated liver enzymes, anaphylactic reaction after the first dose, worsening nephritis, and severe neutropenia.

Overall, 19 patients completed the study. In addition to the five who quit because of adverse events, one additional patient withdrew voluntarily. All had active lupus nephritis of about 50 months’ duration, with a mean daily proteinuria of more than 2 g; about a third of the group had nephrotic proteinuria. The mean Systemic Lupus Erythematosus Disease Activity Index 2000 was about 16. All were taking concomitant mycophenolate mofetil or azathioprine.

At the end of the treatment period, there was no significant between-group difference in proteinuria, Dr. van Vollenhoven said. Four of those in the active group experienced at least a 50% reduction in proteinuria over baseline, while none of those in the placebo group experienced this change. However, this difference was not statistically significant. There were no significant changes in the patient or physical global assessment for either group.

Serious adverse events occurred in 48% of those taking the drug, including serious infections (30%) as well as renal/urinary (19%), blood (9.5%), and gastrointestinal (9.5%) events. None occurred in the placebo group.

Among patients in the sirukumab group, there was one grade 4 lymphocytopenia, one grade 4 neutropenia, and two grade 3 neutropenias. One patient had a grade 2 liver enzyme elevation.

Dr. van Vollenhoven was on the study steering committee and is a consultant and speaker for Janssen, as well as other drug manufacturers. Four coauthors are employees of Janssen.

[email protected]

PARIS – The investigational interleukin-6 blocker sirukumab provided no benefit to patients with lupus nephritis but put them at a very high risk of developing a serious infection in a small, randomized, placebo-controlled trial.

Based on the study results, the study sponsor, Janssen, has shut down its program for the lupus nephritis indication, Dr. Ronald van Vollenhoven said at the annual European Congress of Rheumatology.

"While a few patients did experience a reduction in proteinuria, we had an unacceptably high rate of adverse events," said Dr. van Vollenhoven, chief of the Unit for Clinical Therapy Research, Inflammatory Diseases, at the Karolinska Institute, Stockholm. "Based on these findings, we will not be advancing any further investigation of sirukumab for patients with active lupus nephritis."

The company continues to develop the drug for rheumatoid arthritis.

In the trial, 21 patients received intravenous sirukumab 10 mg/kg once every 4 weeks for 24 weeks, and 4 received placebo. During the trial and a 16-week safety observation follow-up period, 48% of those who took the investigational IL-6 blocker developed a serious adverse event, including infections serious enough to require hospital admission.

While not specifying the infections, which occurred in 10 patients, Dr. van Vollenhoven noted that five patients taking the drug discontinued it because of adverse events, which included Haemophilus influenzae pneumonia, elevated liver enzymes, anaphylactic reaction after the first dose, worsening nephritis, and severe neutropenia.

Overall, 19 patients completed the study. In addition to the five who quit because of adverse events, one additional patient withdrew voluntarily. All had active lupus nephritis of about 50 months’ duration, with a mean daily proteinuria of more than 2 g; about a third of the group had nephrotic proteinuria. The mean Systemic Lupus Erythematosus Disease Activity Index 2000 was about 16. All were taking concomitant mycophenolate mofetil or azathioprine.

At the end of the treatment period, there was no significant between-group difference in proteinuria, Dr. van Vollenhoven said. Four of those in the active group experienced at least a 50% reduction in proteinuria over baseline, while none of those in the placebo group experienced this change. However, this difference was not statistically significant. There were no significant changes in the patient or physical global assessment for either group.

Serious adverse events occurred in 48% of those taking the drug, including serious infections (30%) as well as renal/urinary (19%), blood (9.5%), and gastrointestinal (9.5%) events. None occurred in the placebo group.

Among patients in the sirukumab group, there was one grade 4 lymphocytopenia, one grade 4 neutropenia, and two grade 3 neutropenias. One patient had a grade 2 liver enzyme elevation.

Dr. van Vollenhoven was on the study steering committee and is a consultant and speaker for Janssen, as well as other drug manufacturers. Four coauthors are employees of Janssen.

[email protected]

PARIS – Belimumab produced significant clinical improvement in 74% of patients with systemic lupus erythematosus who took it over a 6-month period, reducing disease symptoms and steroid use and significantly improving quality of life.

Results from the multicenter German OBSErve study paralleled – and even exceeded – those of the BLISS randomized trials, Dr. Andreas Schwarting said at the annual European Congress of Rheumatology.

Michele G. Sullivan/Frontline Medical News

"OBSErve data suggest even greater improvements and lower discontinuation rates in real-world practice," said Dr. Schwarting of the Johannes Gutenberg University of Mainz (Germany). "We also saw a lower discontinuation rate than in the BLISS trials, and our study shows that you can identify responders well within 6 months."

Dr. Schwarting was the lead author of the retrospective, observational study , which included 102 patients with active lupus who were treated with open-label belimumab (Benlysta) over a 6-month period. Most (85%) had moderate or severe disease, and 80% had been on four to five different lupus medications before starting belimumab. The most common reasons for starting belimumab were ineffective prior treatment (88%), worsening disease (61%), and the need to decrease steroid use (40%).

At baseline, the mean steroid dose was 13.7 mg/day; 62% were taking a high dose, with a mean of 17.5 mg/day.

The primary endpoint was overall clinical response after 6 months of treatment. Most (75) had a disease activity improvement of at least 20%, including 35 who had an improvement of up to 49%, 31 with at least a 50% improvement, and 9 with at least an 80% improvement.

Five patients showed no improvement. Two became worse on the medication, and 14 had less than a 20% improvement. Six patients discontinued the drug: three because of disease progression, one because of an allergic reaction, one as a result of a lack of compliance, and one because of heart failure after hospitalization. The patient with heart failure died, but Dr. Schwarting said there was no apparent causal relationship with belimumab.

The improvement occurred in all lupus manifestations, including arthritis (71% response rate), a high level of anti–double-stranded DNA antibodies (50%), low complement levels (34%), fatigue (65%), and rash (62%).

The Systemic Lupus Erythematosus Disease Activity Index scores decreased from a mean of 10.6 to 5.6.

Belimumab exerted a steroid-sparing effect, Dr. Schwarting noted. The mean daily steroid dose decreased from 13.7 mg to 7.6 mg. Among those using more than 17.5 mg/day, the dosage decreased to 8.6 mg/day.

GlaxoSmithKline sponsored the study. Dr. Schwarting said he has received honoraria, consulting, and speakers fees from the company.

[email protected]

On Twitter @alz_gal

PARIS – Belimumab produced significant clinical improvement in 74% of patients with systemic lupus erythematosus who took it over a 6-month period, reducing disease symptoms and steroid use and significantly improving quality of life.

Results from the multicenter German OBSErve study paralleled – and even exceeded – those of the BLISS randomized trials, Dr. Andreas Schwarting said at the annual European Congress of Rheumatology.

Michele G. Sullivan/Frontline Medical News

"OBSErve data suggest even greater improvements and lower discontinuation rates in real-world practice," said Dr. Schwarting of the Johannes Gutenberg University of Mainz (Germany). "We also saw a lower discontinuation rate than in the BLISS trials, and our study shows that you can identify responders well within 6 months."

Dr. Schwarting was the lead author of the retrospective, observational study , which included 102 patients with active lupus who were treated with open-label belimumab (Benlysta) over a 6-month period. Most (85%) had moderate or severe disease, and 80% had been on four to five different lupus medications before starting belimumab. The most common reasons for starting belimumab were ineffective prior treatment (88%), worsening disease (61%), and the need to decrease steroid use (40%).

At baseline, the mean steroid dose was 13.7 mg/day; 62% were taking a high dose, with a mean of 17.5 mg/day.

The primary endpoint was overall clinical response after 6 months of treatment. Most (75) had a disease activity improvement of at least 20%, including 35 who had an improvement of up to 49%, 31 with at least a 50% improvement, and 9 with at least an 80% improvement.

Five patients showed no improvement. Two became worse on the medication, and 14 had less than a 20% improvement. Six patients discontinued the drug: three because of disease progression, one because of an allergic reaction, one as a result of a lack of compliance, and one because of heart failure after hospitalization. The patient with heart failure died, but Dr. Schwarting said there was no apparent causal relationship with belimumab.

The improvement occurred in all lupus manifestations, including arthritis (71% response rate), a high level of anti–double-stranded DNA antibodies (50%), low complement levels (34%), fatigue (65%), and rash (62%).

The Systemic Lupus Erythematosus Disease Activity Index scores decreased from a mean of 10.6 to 5.6.

Belimumab exerted a steroid-sparing effect, Dr. Schwarting noted. The mean daily steroid dose decreased from 13.7 mg to 7.6 mg. Among those using more than 17.5 mg/day, the dosage decreased to 8.6 mg/day.

GlaxoSmithKline sponsored the study. Dr. Schwarting said he has received honoraria, consulting, and speakers fees from the company.

[email protected]

On Twitter @alz_gal

PARIS – Belimumab produced significant clinical improvement in 74% of patients with systemic lupus erythematosus who took it over a 6-month period, reducing disease symptoms and steroid use and significantly improving quality of life.

Results from the multicenter German OBSErve study paralleled – and even exceeded – those of the BLISS randomized trials, Dr. Andreas Schwarting said at the annual European Congress of Rheumatology.

Michele G. Sullivan/Frontline Medical News

"OBSErve data suggest even greater improvements and lower discontinuation rates in real-world practice," said Dr. Schwarting of the Johannes Gutenberg University of Mainz (Germany). "We also saw a lower discontinuation rate than in the BLISS trials, and our study shows that you can identify responders well within 6 months."

Dr. Schwarting was the lead author of the retrospective, observational study , which included 102 patients with active lupus who were treated with open-label belimumab (Benlysta) over a 6-month period. Most (85%) had moderate or severe disease, and 80% had been on four to five different lupus medications before starting belimumab. The most common reasons for starting belimumab were ineffective prior treatment (88%), worsening disease (61%), and the need to decrease steroid use (40%).

At baseline, the mean steroid dose was 13.7 mg/day; 62% were taking a high dose, with a mean of 17.5 mg/day.

The primary endpoint was overall clinical response after 6 months of treatment. Most (75) had a disease activity improvement of at least 20%, including 35 who had an improvement of up to 49%, 31 with at least a 50% improvement, and 9 with at least an 80% improvement.

Five patients showed no improvement. Two became worse on the medication, and 14 had less than a 20% improvement. Six patients discontinued the drug: three because of disease progression, one because of an allergic reaction, one as a result of a lack of compliance, and one because of heart failure after hospitalization. The patient with heart failure died, but Dr. Schwarting said there was no apparent causal relationship with belimumab.

The improvement occurred in all lupus manifestations, including arthritis (71% response rate), a high level of anti–double-stranded DNA antibodies (50%), low complement levels (34%), fatigue (65%), and rash (62%).

The Systemic Lupus Erythematosus Disease Activity Index scores decreased from a mean of 10.6 to 5.6.

Belimumab exerted a steroid-sparing effect, Dr. Schwarting noted. The mean daily steroid dose decreased from 13.7 mg to 7.6 mg. Among those using more than 17.5 mg/day, the dosage decreased to 8.6 mg/day.

GlaxoSmithKline sponsored the study. Dr. Schwarting said he has received honoraria, consulting, and speakers fees from the company.

[email protected]

On Twitter @alz_gal

Large-scale vaccination with a still-unapproved vaccine should be considered if multiple cases of serogroup B meningitis occur within 6 months in a community, a workgroup of the Centers for Disease Control and Prevention recommended June 26.

In groups of fewer than 5,000 people, vaccination should be considered if two or more cases present within 6 months. In larger communities, vaccination may be implemented if three or more cases present over 6 months, Jessica MacNeil said at a meeting of the CDC’s Advisory Committee on Immunization Practices.

Courtesy CDC

The recommendation, which will be posted on the CDC’s meningitis web pages, was developed in response to last year’s group B meningitis outbreaks at the University of California, Santa Barbara, and at Princeton University, said Ms. MacNeil, an epidemiologist at the CDC and liaison with ACIP’s Meningococcal Outbreak Working Group.

When the outbreaks occurred, the CDC sponsored an expanded-access Investigational New Drug (IND) application so that students at both campuses could receive the unapproved vaccine.

The workgroup was convened in January and has conducted biweekly meetings to develop some interim guidance that would allow prompt response to future outbreaks in the absence of an approved vaccine.

"There are delays in getting a vaccination campaign in place under an IND," Ms. MacNeil said. "Therefore, we need to consider options early. We recognize that waiting for additional cases to occur before acting is difficult for organizations, so we need to have clear steps for each case already identified."

The proposed guideline begins with testing clinical specimens of Neisseria meningitides. Serogrouping should be initiated with 24 hours of collection. Labs that can’t do so within 72 hours need to transfer the specimen to a lab that can or get samples to the CDC within 24 hours.

The CDC will work with state and local health departments in determining whether or not a large-scale vaccination is appropriate. That decision involves several considerations: the number of cases, the size of the community involved, the strains present in the cases, the feasibility and cost of vaccinating, and vaccine availability.

For groups of fewer than 5,000, one case of meningitis should activate routine public health practices: serogrouping, a case investigation, and chemoprophylaxis for close contacts. The isolates should be saved.

Once two or more cases have been identified, specimens should be sent to the CDC for molecular genotyping. If they are identified as serogroup B and, thus, likely to be covered by the MenB vaccine, local health officials may consult with CDC about using the vaccine under the expanded access IND program.

In communities of 5,000 or more, a single case will prompt the same routine public health practices. If two cases occur within 6 months, the isolates should be tested. If they are both serogroup B, the CDC should be notified and the situation carefully monitored. If three or more cases develop and the isolates are all serogroup B, then the IND vaccination campaign can be considered.

If the CDC-sponsored IND is activated, any organization that provides the vaccine must appoint a local coinvestigator. The group will be required to participate in safety follow-up studies as required by the program.

Ms. MacNeil added that the universities that have implemented MenB vaccination campaigns are bearing the cost of obtaining and administering the vaccine.

She also discussed the value of large-scale chemoprophylaxis. A literature review identified 18 instances in which mass chemoprophylaxis had been used as an outbreak response. These suggested that chemoprophylaxis resulted in decreases in carriage soon after, but no permanent clearance.

"Mass chemoprophylaxis is not recommended as a stand-alone measure to control outbreaks of meningococcal disease," she said. "It may be considered as an interim measure to reduce carriage and transmission in the period before potential protection from vaccination can be achieved."

However, she added, chemoprophylaxis only would be effective in small or closed populations with limited mixing from the outside – like jails or residential facilities.

"It would be difficult to ensure that everyone in the target group could receive treatment within a short time frame," she said. And dosing everyone in a population opens up the possibility of idiosyncratic adverse reactions and interactions with other commonly used medications, including antidepressants.

"In many outbreak settings, particularly when a small, closed, at-risk population can’t be defined, the disadvantages outweigh the possible benefits," she said.

She said the guidance will be published within a few days on the CDC’s meningitis pages.

[email protected]

Large-scale vaccination with a still-unapproved vaccine should be considered if multiple cases of serogroup B meningitis occur within 6 months in a community, a workgroup of the Centers for Disease Control and Prevention recommended June 26.

In groups of fewer than 5,000 people, vaccination should be considered if two or more cases present within 6 months. In larger communities, vaccination may be implemented if three or more cases present over 6 months, Jessica MacNeil said at a meeting of the CDC’s Advisory Committee on Immunization Practices.

Courtesy CDC

The recommendation, which will be posted on the CDC’s meningitis web pages, was developed in response to last year’s group B meningitis outbreaks at the University of California, Santa Barbara, and at Princeton University, said Ms. MacNeil, an epidemiologist at the CDC and liaison with ACIP’s Meningococcal Outbreak Working Group.

When the outbreaks occurred, the CDC sponsored an expanded-access Investigational New Drug (IND) application so that students at both campuses could receive the unapproved vaccine.

The workgroup was convened in January and has conducted biweekly meetings to develop some interim guidance that would allow prompt response to future outbreaks in the absence of an approved vaccine.

"There are delays in getting a vaccination campaign in place under an IND," Ms. MacNeil said. "Therefore, we need to consider options early. We recognize that waiting for additional cases to occur before acting is difficult for organizations, so we need to have clear steps for each case already identified."

The proposed guideline begins with testing clinical specimens of Neisseria meningitides. Serogrouping should be initiated with 24 hours of collection. Labs that can’t do so within 72 hours need to transfer the specimen to a lab that can or get samples to the CDC within 24 hours.

The CDC will work with state and local health departments in determining whether or not a large-scale vaccination is appropriate. That decision involves several considerations: the number of cases, the size of the community involved, the strains present in the cases, the feasibility and cost of vaccinating, and vaccine availability.

For groups of fewer than 5,000, one case of meningitis should activate routine public health practices: serogrouping, a case investigation, and chemoprophylaxis for close contacts. The isolates should be saved.

Once two or more cases have been identified, specimens should be sent to the CDC for molecular genotyping. If they are identified as serogroup B and, thus, likely to be covered by the MenB vaccine, local health officials may consult with CDC about using the vaccine under the expanded access IND program.

In communities of 5,000 or more, a single case will prompt the same routine public health practices. If two cases occur within 6 months, the isolates should be tested. If they are both serogroup B, the CDC should be notified and the situation carefully monitored. If three or more cases develop and the isolates are all serogroup B, then the IND vaccination campaign can be considered.

If the CDC-sponsored IND is activated, any organization that provides the vaccine must appoint a local coinvestigator. The group will be required to participate in safety follow-up studies as required by the program.

Ms. MacNeil added that the universities that have implemented MenB vaccination campaigns are bearing the cost of obtaining and administering the vaccine.

She also discussed the value of large-scale chemoprophylaxis. A literature review identified 18 instances in which mass chemoprophylaxis had been used as an outbreak response. These suggested that chemoprophylaxis resulted in decreases in carriage soon after, but no permanent clearance.

"Mass chemoprophylaxis is not recommended as a stand-alone measure to control outbreaks of meningococcal disease," she said. "It may be considered as an interim measure to reduce carriage and transmission in the period before potential protection from vaccination can be achieved."

However, she added, chemoprophylaxis only would be effective in small or closed populations with limited mixing from the outside – like jails or residential facilities.

"It would be difficult to ensure that everyone in the target group could receive treatment within a short time frame," she said. And dosing everyone in a population opens up the possibility of idiosyncratic adverse reactions and interactions with other commonly used medications, including antidepressants.

"In many outbreak settings, particularly when a small, closed, at-risk population can’t be defined, the disadvantages outweigh the possible benefits," she said.

She said the guidance will be published within a few days on the CDC’s meningitis pages.

[email protected]

Large-scale vaccination with a still-unapproved vaccine should be considered if multiple cases of serogroup B meningitis occur within 6 months in a community, a workgroup of the Centers for Disease Control and Prevention recommended June 26.

In groups of fewer than 5,000 people, vaccination should be considered if two or more cases present within 6 months. In larger communities, vaccination may be implemented if three or more cases present over 6 months, Jessica MacNeil said at a meeting of the CDC’s Advisory Committee on Immunization Practices.

Courtesy CDC

The recommendation, which will be posted on the CDC’s meningitis web pages, was developed in response to last year’s group B meningitis outbreaks at the University of California, Santa Barbara, and at Princeton University, said Ms. MacNeil, an epidemiologist at the CDC and liaison with ACIP’s Meningococcal Outbreak Working Group.

When the outbreaks occurred, the CDC sponsored an expanded-access Investigational New Drug (IND) application so that students at both campuses could receive the unapproved vaccine.

The workgroup was convened in January and has conducted biweekly meetings to develop some interim guidance that would allow prompt response to future outbreaks in the absence of an approved vaccine.

"There are delays in getting a vaccination campaign in place under an IND," Ms. MacNeil said. "Therefore, we need to consider options early. We recognize that waiting for additional cases to occur before acting is difficult for organizations, so we need to have clear steps for each case already identified."

The proposed guideline begins with testing clinical specimens of Neisseria meningitides. Serogrouping should be initiated with 24 hours of collection. Labs that can’t do so within 72 hours need to transfer the specimen to a lab that can or get samples to the CDC within 24 hours.

The CDC will work with state and local health departments in determining whether or not a large-scale vaccination is appropriate. That decision involves several considerations: the number of cases, the size of the community involved, the strains present in the cases, the feasibility and cost of vaccinating, and vaccine availability.

For groups of fewer than 5,000, one case of meningitis should activate routine public health practices: serogrouping, a case investigation, and chemoprophylaxis for close contacts. The isolates should be saved.

Once two or more cases have been identified, specimens should be sent to the CDC for molecular genotyping. If they are identified as serogroup B and, thus, likely to be covered by the MenB vaccine, local health officials may consult with CDC about using the vaccine under the expanded access IND program.

In communities of 5,000 or more, a single case will prompt the same routine public health practices. If two cases occur within 6 months, the isolates should be tested. If they are both serogroup B, the CDC should be notified and the situation carefully monitored. If three or more cases develop and the isolates are all serogroup B, then the IND vaccination campaign can be considered.

If the CDC-sponsored IND is activated, any organization that provides the vaccine must appoint a local coinvestigator. The group will be required to participate in safety follow-up studies as required by the program.

Ms. MacNeil added that the universities that have implemented MenB vaccination campaigns are bearing the cost of obtaining and administering the vaccine.

She also discussed the value of large-scale chemoprophylaxis. A literature review identified 18 instances in which mass chemoprophylaxis had been used as an outbreak response. These suggested that chemoprophylaxis resulted in decreases in carriage soon after, but no permanent clearance.

"Mass chemoprophylaxis is not recommended as a stand-alone measure to control outbreaks of meningococcal disease," she said. "It may be considered as an interim measure to reduce carriage and transmission in the period before potential protection from vaccination can be achieved."

However, she added, chemoprophylaxis only would be effective in small or closed populations with limited mixing from the outside – like jails or residential facilities.

"It would be difficult to ensure that everyone in the target group could receive treatment within a short time frame," she said. And dosing everyone in a population opens up the possibility of idiosyncratic adverse reactions and interactions with other commonly used medications, including antidepressants.

"In many outbreak settings, particularly when a small, closed, at-risk population can’t be defined, the disadvantages outweigh the possible benefits," she said.

She said the guidance will be published within a few days on the CDC’s meningitis pages.

[email protected]