The Pulmonary Fibrosis Foundation (PFF) has begun offering a tool to help patients navigate through more than 100 clinical trials aimed at advancing the treatment of pulmonary fibrosis, according to a statement from the Foundation.

The new tool, the PFF Clinical Trial Finder allows patients “to filter trials by general categories and locations.” The platform includes trials for patients with idiopathic pulmonary fibrosis.

“Before this, it was pretty impossible to search for clinical trials,” noted Bill Burke, a PF patient and support group leader from Williamsburg, Va., in the statement.

The tool, which is available both on the PFF website and as a free app, draws on information from ClinicalTrials.gov.

The Foundation intends for the new tool to give patients “a voice in their care process,” according to the statement.

“We want to empower patients to actively participate in identifying clinical trials,” said Harold R. Collard, MD, senior medical adviser of research and development for the Pulmonary Fibrosis Foundation.

More information about the trial finder is available on the PFF’s website.

[email protected]

The Pulmonary Fibrosis Foundation (PFF) has begun offering a tool to help patients navigate through more than 100 clinical trials aimed at advancing the treatment of pulmonary fibrosis, according to a statement from the Foundation.

The new tool, the PFF Clinical Trial Finder allows patients “to filter trials by general categories and locations.” The platform includes trials for patients with idiopathic pulmonary fibrosis.

“Before this, it was pretty impossible to search for clinical trials,” noted Bill Burke, a PF patient and support group leader from Williamsburg, Va., in the statement.

The tool, which is available both on the PFF website and as a free app, draws on information from ClinicalTrials.gov.

The Foundation intends for the new tool to give patients “a voice in their care process,” according to the statement.

“We want to empower patients to actively participate in identifying clinical trials,” said Harold R. Collard, MD, senior medical adviser of research and development for the Pulmonary Fibrosis Foundation.

More information about the trial finder is available on the PFF’s website.

[email protected]

The Pulmonary Fibrosis Foundation (PFF) has begun offering a tool to help patients navigate through more than 100 clinical trials aimed at advancing the treatment of pulmonary fibrosis, according to a statement from the Foundation.

The new tool, the PFF Clinical Trial Finder allows patients “to filter trials by general categories and locations.” The platform includes trials for patients with idiopathic pulmonary fibrosis.

“Before this, it was pretty impossible to search for clinical trials,” noted Bill Burke, a PF patient and support group leader from Williamsburg, Va., in the statement.

The tool, which is available both on the PFF website and as a free app, draws on information from ClinicalTrials.gov.

The Foundation intends for the new tool to give patients “a voice in their care process,” according to the statement.

“We want to empower patients to actively participate in identifying clinical trials,” said Harold R. Collard, MD, senior medical adviser of research and development for the Pulmonary Fibrosis Foundation.

More information about the trial finder is available on the PFF’s website.

[email protected]

Mogamulizumab reduced the number of HTLV-1–infected cells and levels of inflammatory markers in patients with HTLV-1–associated myelopathy–tropical spastic paraparesis (HAM-TSP) in a recently reported phase 1-2a study.

Treatment with the anti-CCR4 monoclonal antibody also reduced spasticity and motor disability in some patients with HAM-TSP, according to results published in the New England Journal of Medicine.

Rash was the main side effect of treatment, but the 21-patient trial was “too small and too short to evaluate the clinical safety of mogamulizumab,” said lead author Tomoo Sato, MD, PhD, of the Department of Rare Diseases Research, St. Marianna University, Kawasaki, Japan, and colleagues.

HAM-TSP is a chronic, progressive, and debilitating neuroinflammatory disorder primarily seen in equatorial regions, according to the National Institute of Neurological Disorders and Stroke.

HTVL-1 infects primarily CCR4+ T cells, and mogamulizumab is an anti-CCR4 antibody that targets those affected cells, according to Dr. Sato and colleagues.

Current treatment for HAM-TSP is typically focused on suppressing inflammation with glucocorticoid or interferon-alpha rather than attacking infected cells and reducing proviral load.

The current investigator-initiated study included 21 patients with glucocorticoid-refractory HAM-TSP. In phase 1 of the study, patients received a single intravenous infusion of mogamulizumab and were observed for 85 days. Of those patients, 19 continued to phase 2a and received infusions at 8- or 12-week intervals for a total of 24 weeks.

Treatment resulted in a reduction of 64.9% (95% confidence interval, 51.7-78.1) in proviral load in peripheral-blood mononuclear cells by day 15 postinfusion. Reductions in inflammatory markers at day 29 were also reported, including a 37.3% decrease in CXCL10 levels and a 21.0% decrease in neopterin levels.

In all, 79% of patients had a reduction in spasticity, and 32% had decreased motor disability after treatment.

“The clinical effects appeared very quickly, long before any changes in the markers of inflammation in the central nervous system,” the investigators said.

Grade 1 or 2 rash was seen in 48% of patients, while lymphopenia and leukopenia were seen in 33% of patients each.

A phase 2 study is ongoing to evaluate the long-term safety and efficacy of mogamulizumab in patients with HAM-TSP.

The study was supported by the Japan Agency for Medical Research and Development and by the Ministry of Health, Labor, and Welfare. Two of the coauthors reported patents related to treating HTLV-I–related myelopathy.

SOURCE: Sato T et al. N Engl J Med. 2018;378:529-38.

Mogamulizumab reduced the number of HTLV-1–infected cells and levels of inflammatory markers in patients with HTLV-1–associated myelopathy–tropical spastic paraparesis (HAM-TSP) in a recently reported phase 1-2a study.

Treatment with the anti-CCR4 monoclonal antibody also reduced spasticity and motor disability in some patients with HAM-TSP, according to results published in the New England Journal of Medicine.

Rash was the main side effect of treatment, but the 21-patient trial was “too small and too short to evaluate the clinical safety of mogamulizumab,” said lead author Tomoo Sato, MD, PhD, of the Department of Rare Diseases Research, St. Marianna University, Kawasaki, Japan, and colleagues.

HAM-TSP is a chronic, progressive, and debilitating neuroinflammatory disorder primarily seen in equatorial regions, according to the National Institute of Neurological Disorders and Stroke.

HTVL-1 infects primarily CCR4+ T cells, and mogamulizumab is an anti-CCR4 antibody that targets those affected cells, according to Dr. Sato and colleagues.

Current treatment for HAM-TSP is typically focused on suppressing inflammation with glucocorticoid or interferon-alpha rather than attacking infected cells and reducing proviral load.

The current investigator-initiated study included 21 patients with glucocorticoid-refractory HAM-TSP. In phase 1 of the study, patients received a single intravenous infusion of mogamulizumab and were observed for 85 days. Of those patients, 19 continued to phase 2a and received infusions at 8- or 12-week intervals for a total of 24 weeks.

Treatment resulted in a reduction of 64.9% (95% confidence interval, 51.7-78.1) in proviral load in peripheral-blood mononuclear cells by day 15 postinfusion. Reductions in inflammatory markers at day 29 were also reported, including a 37.3% decrease in CXCL10 levels and a 21.0% decrease in neopterin levels.

In all, 79% of patients had a reduction in spasticity, and 32% had decreased motor disability after treatment.

“The clinical effects appeared very quickly, long before any changes in the markers of inflammation in the central nervous system,” the investigators said.

Grade 1 or 2 rash was seen in 48% of patients, while lymphopenia and leukopenia were seen in 33% of patients each.

A phase 2 study is ongoing to evaluate the long-term safety and efficacy of mogamulizumab in patients with HAM-TSP.

The study was supported by the Japan Agency for Medical Research and Development and by the Ministry of Health, Labor, and Welfare. Two of the coauthors reported patents related to treating HTLV-I–related myelopathy.

SOURCE: Sato T et al. N Engl J Med. 2018;378:529-38.

Mogamulizumab reduced the number of HTLV-1–infected cells and levels of inflammatory markers in patients with HTLV-1–associated myelopathy–tropical spastic paraparesis (HAM-TSP) in a recently reported phase 1-2a study.

Treatment with the anti-CCR4 monoclonal antibody also reduced spasticity and motor disability in some patients with HAM-TSP, according to results published in the New England Journal of Medicine.

Rash was the main side effect of treatment, but the 21-patient trial was “too small and too short to evaluate the clinical safety of mogamulizumab,” said lead author Tomoo Sato, MD, PhD, of the Department of Rare Diseases Research, St. Marianna University, Kawasaki, Japan, and colleagues.

HAM-TSP is a chronic, progressive, and debilitating neuroinflammatory disorder primarily seen in equatorial regions, according to the National Institute of Neurological Disorders and Stroke.

HTVL-1 infects primarily CCR4+ T cells, and mogamulizumab is an anti-CCR4 antibody that targets those affected cells, according to Dr. Sato and colleagues.

Current treatment for HAM-TSP is typically focused on suppressing inflammation with glucocorticoid or interferon-alpha rather than attacking infected cells and reducing proviral load.

The current investigator-initiated study included 21 patients with glucocorticoid-refractory HAM-TSP. In phase 1 of the study, patients received a single intravenous infusion of mogamulizumab and were observed for 85 days. Of those patients, 19 continued to phase 2a and received infusions at 8- or 12-week intervals for a total of 24 weeks.

Treatment resulted in a reduction of 64.9% (95% confidence interval, 51.7-78.1) in proviral load in peripheral-blood mononuclear cells by day 15 postinfusion. Reductions in inflammatory markers at day 29 were also reported, including a 37.3% decrease in CXCL10 levels and a 21.0% decrease in neopterin levels.

In all, 79% of patients had a reduction in spasticity, and 32% had decreased motor disability after treatment.

“The clinical effects appeared very quickly, long before any changes in the markers of inflammation in the central nervous system,” the investigators said.

Grade 1 or 2 rash was seen in 48% of patients, while lymphopenia and leukopenia were seen in 33% of patients each.

A phase 2 study is ongoing to evaluate the long-term safety and efficacy of mogamulizumab in patients with HAM-TSP.

The study was supported by the Japan Agency for Medical Research and Development and by the Ministry of Health, Labor, and Welfare. Two of the coauthors reported patents related to treating HTLV-I–related myelopathy.

SOURCE: Sato T et al. N Engl J Med. 2018;378:529-38.

LAS VEGAS – High levels of patient activation are associated with clinical remission in patients with inflammatory bowel disease, results from a longitudinal analysis suggest.

“Patient activation is defined as understanding one’s role in the health care process and having the knowledge, skills, and confidence to manage one’s health,” Edward L. Barnes, MD, MPH, said at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “It emphasizes an individual’s willingness to take independent actions and manage their own health care. In many chronic conditions, higher levels of patient activation have been linked to improved health outcomes, better patient experiences related to health care, higher quality of life scores, and lower overall health care costs.”

High patient activation was defined as level 3 or level 4 on the Patient Activation Measure, and multivariable logistic regression was used to evaluate predictors of patient activation level and the relationship between level of patient activation and clinical remission. All covariates included in the multivariable analyses were identified a priori based on prior association with patient activation or clinical disease activity in IBD.

The survey was administered to 1,486 participants. Of these, 1,082 (73%) completed follow-up surveys, including assessments of disease activity. The mean age of respondents was 44 years, 74% were female, 5% were nonwhite, and 77% reported their highest education level as college or graduate school. The mean disease duration was 14.4 years.

Patients with less than a 12th grade education were significantly associated with a decreased odds of having patient activation (adjusted odds ratio 0.25 [95% confidence interval, 0.07-0.94]). Although nonsignificant after adjustment for potential confounders, nonwhite race was also associated with decreased odds of high patient activation (aOR 0.64). Meanwhile, there was a trend among those who graduated from college or graduate school in predicting high patient activation level (aOR of 1.44 and 1.36, respectively).

After adjustment for race, educational status, time since diagnosis, smoking status, and history of IBD-related surgery among patients with Crohn’s disease, patients with higher patient activation were more likely to be in clinical remission at follow-up for both Crohn’s disease (71% vs. 62%; aOR of 1.60 [95% CI, 1.00-2.57], P = .05) and ulcerative colitis (54% vs. 34%; aOR 2.23, respectively; [95% CI, 1.15-4.19], P = .01).

Dr. Barnes acknowledged certain limitations of the study, including the fact that study participants comprised a voluntary, Internet-based cohort. “Participants may exhibit higher levels of patient activation than the general population of patients with IBD,” he said. “There may be an overrepresentation of college graduates in this sample, and the racial and ethnic makeup of this cohort may be different from that of a clinic-based population or the general population of patients with IBD.” He added that there might be unmeasured confounders in the relationship between patient activation and remission that the researchers could not assess.

“Patient activation appears to impact the disease course in patients with CD [Crohn’s disease] and UC [ulcerative colitis],” Dr. Barnes concluded. “The effect of patient activation on the disease course may be larger in UC than in CD. Efforts to improve patient activation in patients with IBD may have the ability to ultimately improve clinical outcomes.”

He reported having no financial disclosures.

*This story was updated on 3/26.

[email protected]

SOURCE: Barnes EL et al. Crohn’s & Colitis Congress, Clinical Abstract 12.

LAS VEGAS – High levels of patient activation are associated with clinical remission in patients with inflammatory bowel disease, results from a longitudinal analysis suggest.

“Patient activation is defined as understanding one’s role in the health care process and having the knowledge, skills, and confidence to manage one’s health,” Edward L. Barnes, MD, MPH, said at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “It emphasizes an individual’s willingness to take independent actions and manage their own health care. In many chronic conditions, higher levels of patient activation have been linked to improved health outcomes, better patient experiences related to health care, higher quality of life scores, and lower overall health care costs.”

High patient activation was defined as level 3 or level 4 on the Patient Activation Measure, and multivariable logistic regression was used to evaluate predictors of patient activation level and the relationship between level of patient activation and clinical remission. All covariates included in the multivariable analyses were identified a priori based on prior association with patient activation or clinical disease activity in IBD.

The survey was administered to 1,486 participants. Of these, 1,082 (73%) completed follow-up surveys, including assessments of disease activity. The mean age of respondents was 44 years, 74% were female, 5% were nonwhite, and 77% reported their highest education level as college or graduate school. The mean disease duration was 14.4 years.

Patients with less than a 12th grade education were significantly associated with a decreased odds of having patient activation (adjusted odds ratio 0.25 [95% confidence interval, 0.07-0.94]). Although nonsignificant after adjustment for potential confounders, nonwhite race was also associated with decreased odds of high patient activation (aOR 0.64). Meanwhile, there was a trend among those who graduated from college or graduate school in predicting high patient activation level (aOR of 1.44 and 1.36, respectively).

After adjustment for race, educational status, time since diagnosis, smoking status, and history of IBD-related surgery among patients with Crohn’s disease, patients with higher patient activation were more likely to be in clinical remission at follow-up for both Crohn’s disease (71% vs. 62%; aOR of 1.60 [95% CI, 1.00-2.57], P = .05) and ulcerative colitis (54% vs. 34%; aOR 2.23, respectively; [95% CI, 1.15-4.19], P = .01).

Dr. Barnes acknowledged certain limitations of the study, including the fact that study participants comprised a voluntary, Internet-based cohort. “Participants may exhibit higher levels of patient activation than the general population of patients with IBD,” he said. “There may be an overrepresentation of college graduates in this sample, and the racial and ethnic makeup of this cohort may be different from that of a clinic-based population or the general population of patients with IBD.” He added that there might be unmeasured confounders in the relationship between patient activation and remission that the researchers could not assess.

“Patient activation appears to impact the disease course in patients with CD [Crohn’s disease] and UC [ulcerative colitis],” Dr. Barnes concluded. “The effect of patient activation on the disease course may be larger in UC than in CD. Efforts to improve patient activation in patients with IBD may have the ability to ultimately improve clinical outcomes.”

He reported having no financial disclosures.

*This story was updated on 3/26.

[email protected]

SOURCE: Barnes EL et al. Crohn’s & Colitis Congress, Clinical Abstract 12.

LAS VEGAS – High levels of patient activation are associated with clinical remission in patients with inflammatory bowel disease, results from a longitudinal analysis suggest.

“Patient activation is defined as understanding one’s role in the health care process and having the knowledge, skills, and confidence to manage one’s health,” Edward L. Barnes, MD, MPH, said at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “It emphasizes an individual’s willingness to take independent actions and manage their own health care. In many chronic conditions, higher levels of patient activation have been linked to improved health outcomes, better patient experiences related to health care, higher quality of life scores, and lower overall health care costs.”

High patient activation was defined as level 3 or level 4 on the Patient Activation Measure, and multivariable logistic regression was used to evaluate predictors of patient activation level and the relationship between level of patient activation and clinical remission. All covariates included in the multivariable analyses were identified a priori based on prior association with patient activation or clinical disease activity in IBD.

The survey was administered to 1,486 participants. Of these, 1,082 (73%) completed follow-up surveys, including assessments of disease activity. The mean age of respondents was 44 years, 74% were female, 5% were nonwhite, and 77% reported their highest education level as college or graduate school. The mean disease duration was 14.4 years.

Patients with less than a 12th grade education were significantly associated with a decreased odds of having patient activation (adjusted odds ratio 0.25 [95% confidence interval, 0.07-0.94]). Although nonsignificant after adjustment for potential confounders, nonwhite race was also associated with decreased odds of high patient activation (aOR 0.64). Meanwhile, there was a trend among those who graduated from college or graduate school in predicting high patient activation level (aOR of 1.44 and 1.36, respectively).

After adjustment for race, educational status, time since diagnosis, smoking status, and history of IBD-related surgery among patients with Crohn’s disease, patients with higher patient activation were more likely to be in clinical remission at follow-up for both Crohn’s disease (71% vs. 62%; aOR of 1.60 [95% CI, 1.00-2.57], P = .05) and ulcerative colitis (54% vs. 34%; aOR 2.23, respectively; [95% CI, 1.15-4.19], P = .01).

Dr. Barnes acknowledged certain limitations of the study, including the fact that study participants comprised a voluntary, Internet-based cohort. “Participants may exhibit higher levels of patient activation than the general population of patients with IBD,” he said. “There may be an overrepresentation of college graduates in this sample, and the racial and ethnic makeup of this cohort may be different from that of a clinic-based population or the general population of patients with IBD.” He added that there might be unmeasured confounders in the relationship between patient activation and remission that the researchers could not assess.

“Patient activation appears to impact the disease course in patients with CD [Crohn’s disease] and UC [ulcerative colitis],” Dr. Barnes concluded. “The effect of patient activation on the disease course may be larger in UC than in CD. Efforts to improve patient activation in patients with IBD may have the ability to ultimately improve clinical outcomes.”

He reported having no financial disclosures.

*This story was updated on 3/26.

[email protected]

SOURCE: Barnes EL et al. Crohn’s & Colitis Congress, Clinical Abstract 12.

LOS ANGELES – A postmarketing study of the Wingspan stent shows that the safety of the device in the treatment of intracranial atherosclerotic disease (ICAD) is good enough to be a reasonable alternative to medical management in these patients, but only if the device is used on label.

The results may reassure some interventionalists who were alarmed by results from the Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (N Engl J Med. 2011;365:993-1003), which showed a 30-day rate of stroke or death of 14.7%. The new study showed a frequency of 2.6%, so long as the device was used on label. Off-label use yielded a frequency of 23.9%.

pixologicstudio/Thinkstock.com

The SAMMPRIS findings put a damper on stenting, and use of the procedure has dropped at many U.S. hospitals. But studies conducted prior to SAMMPRIS had shown much lower periprocedural morbidity, and those studies looked at on-label use of stenting. SAMMPRIS was off label.

Now the WEAVE study, which was an Food and Drug Administration–mandated, postmarketing surveillance study of Stryker’s Wingspan stent, suggests that the off-label use of the system in the SAMMPRIS trial may explain the poor results. SAMMPRIS had attempted to extend the approved boundaries of stenting by treating patients who presented with transient ischemic attacks only, patients who had failed medical therapy, and patients who had experienced a stroke in the past 7 days. In fact, about half of the patients were treated within 7 days of the previous event, sometimes within 24 hours.

Previous studies had shown that risk factors for poor outcomes included stenting within 10 days of the last event, stenting a posterior circulation target lesion, stenting presentations other than stroke, and sites with a low patient volume for stenting. Patient selection is vital to success, according to Dr. Alexander. Patients with hemodynamic compromise are good candidates for stenting, while those with perforator stroke alone are better off with medical therapy. Embolic stroke patients are candidates for either approach.

WEAVE looked at 152 consecutive patients treated on label at 24 institutions. The primary analysis group consisted of patients with a 70%-99% stenotic intracranial atherosclerotic lesion who were refractory to medical treatment, 22-80 years of age, and had a modified Rankin Scale (mRS) score of 3 or less at baseline. The treatment was performed at least 7 days after the last stroke. Finally, patients had to have experienced two or more strokes. This last requirement presented a problem for recruitment, according to Dr. Alexander. “That was never a criterion for any of the [previous] trials, so it’s not clear why FDA added that. That made it very difficult to enroll for this trial – to have patients who had two or more strokes and still had a functional mRS score,” he said.

The study protocol aimed for a frequency of 6.6% for periprocedural morbidity, defined as a stroke or death within 72 hours.

An interim analysis at 100 patients showed that the periprocedural morbidity frequency was below 4%, which met the agency’s requirement and allowed the trial to be halted once the trial enrolled 150 on-label patients. The total number of on-label patients reached 152, and the researchers analyzed the results from another 46 patients who were treated with stenting despite not meeting the study’s inclusion criteria, and these patients were considered to be off-label use. The final analysis showed that the on-label group had a periprocedural morbidity of 2.6%, compared with 23.9% in the off-label group (P = .0001).

The most glaring difference in the patient populations was that half of the off-label group received the stent within 7 days of experiencing a stroke. What might be the reason for worse outcomes when stenting is performed within 7 days? “There’s speculation that the plaques might be hot, and those patients might have a higher thrombotic risk with putting a foreign body in the vessel, or there’s capillary instability, so reperfusing a vessel that has a 99% stenosis has a higher risk for reperfusion hemorrhage,” Dr. Alexander said.

Experience may also be a factor. Interventionalists participating in the WEAVE trial had performed a stent using Wingspan an average of 37 times before the study began, compared with a mean of 10 cases for physicians in the SAMMPRIS trial. Those who had performed over 50 procedures had no periprocedural morbidity outcomes at all.

The study was funded by Stryker Neurovascular. Dr. Alexander has consulted for Stryker.

SOURCE: Alexander M et al. ISC 2018 Abstract LB13.

LOS ANGELES – A postmarketing study of the Wingspan stent shows that the safety of the device in the treatment of intracranial atherosclerotic disease (ICAD) is good enough to be a reasonable alternative to medical management in these patients, but only if the device is used on label.

The results may reassure some interventionalists who were alarmed by results from the Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (N Engl J Med. 2011;365:993-1003), which showed a 30-day rate of stroke or death of 14.7%. The new study showed a frequency of 2.6%, so long as the device was used on label. Off-label use yielded a frequency of 23.9%.

pixologicstudio/Thinkstock.com

The SAMMPRIS findings put a damper on stenting, and use of the procedure has dropped at many U.S. hospitals. But studies conducted prior to SAMMPRIS had shown much lower periprocedural morbidity, and those studies looked at on-label use of stenting. SAMMPRIS was off label.

Now the WEAVE study, which was an Food and Drug Administration–mandated, postmarketing surveillance study of Stryker’s Wingspan stent, suggests that the off-label use of the system in the SAMMPRIS trial may explain the poor results. SAMMPRIS had attempted to extend the approved boundaries of stenting by treating patients who presented with transient ischemic attacks only, patients who had failed medical therapy, and patients who had experienced a stroke in the past 7 days. In fact, about half of the patients were treated within 7 days of the previous event, sometimes within 24 hours.

Previous studies had shown that risk factors for poor outcomes included stenting within 10 days of the last event, stenting a posterior circulation target lesion, stenting presentations other than stroke, and sites with a low patient volume for stenting. Patient selection is vital to success, according to Dr. Alexander. Patients with hemodynamic compromise are good candidates for stenting, while those with perforator stroke alone are better off with medical therapy. Embolic stroke patients are candidates for either approach.

WEAVE looked at 152 consecutive patients treated on label at 24 institutions. The primary analysis group consisted of patients with a 70%-99% stenotic intracranial atherosclerotic lesion who were refractory to medical treatment, 22-80 years of age, and had a modified Rankin Scale (mRS) score of 3 or less at baseline. The treatment was performed at least 7 days after the last stroke. Finally, patients had to have experienced two or more strokes. This last requirement presented a problem for recruitment, according to Dr. Alexander. “That was never a criterion for any of the [previous] trials, so it’s not clear why FDA added that. That made it very difficult to enroll for this trial – to have patients who had two or more strokes and still had a functional mRS score,” he said.

The study protocol aimed for a frequency of 6.6% for periprocedural morbidity, defined as a stroke or death within 72 hours.

An interim analysis at 100 patients showed that the periprocedural morbidity frequency was below 4%, which met the agency’s requirement and allowed the trial to be halted once the trial enrolled 150 on-label patients. The total number of on-label patients reached 152, and the researchers analyzed the results from another 46 patients who were treated with stenting despite not meeting the study’s inclusion criteria, and these patients were considered to be off-label use. The final analysis showed that the on-label group had a periprocedural morbidity of 2.6%, compared with 23.9% in the off-label group (P = .0001).

The most glaring difference in the patient populations was that half of the off-label group received the stent within 7 days of experiencing a stroke. What might be the reason for worse outcomes when stenting is performed within 7 days? “There’s speculation that the plaques might be hot, and those patients might have a higher thrombotic risk with putting a foreign body in the vessel, or there’s capillary instability, so reperfusing a vessel that has a 99% stenosis has a higher risk for reperfusion hemorrhage,” Dr. Alexander said.

Experience may also be a factor. Interventionalists participating in the WEAVE trial had performed a stent using Wingspan an average of 37 times before the study began, compared with a mean of 10 cases for physicians in the SAMMPRIS trial. Those who had performed over 50 procedures had no periprocedural morbidity outcomes at all.

The study was funded by Stryker Neurovascular. Dr. Alexander has consulted for Stryker.

SOURCE: Alexander M et al. ISC 2018 Abstract LB13.

LOS ANGELES – A postmarketing study of the Wingspan stent shows that the safety of the device in the treatment of intracranial atherosclerotic disease (ICAD) is good enough to be a reasonable alternative to medical management in these patients, but only if the device is used on label.

The results may reassure some interventionalists who were alarmed by results from the Stenting versus Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial (N Engl J Med. 2011;365:993-1003), which showed a 30-day rate of stroke or death of 14.7%. The new study showed a frequency of 2.6%, so long as the device was used on label. Off-label use yielded a frequency of 23.9%.

pixologicstudio/Thinkstock.com

The SAMMPRIS findings put a damper on stenting, and use of the procedure has dropped at many U.S. hospitals. But studies conducted prior to SAMMPRIS had shown much lower periprocedural morbidity, and those studies looked at on-label use of stenting. SAMMPRIS was off label.

Now the WEAVE study, which was an Food and Drug Administration–mandated, postmarketing surveillance study of Stryker’s Wingspan stent, suggests that the off-label use of the system in the SAMMPRIS trial may explain the poor results. SAMMPRIS had attempted to extend the approved boundaries of stenting by treating patients who presented with transient ischemic attacks only, patients who had failed medical therapy, and patients who had experienced a stroke in the past 7 days. In fact, about half of the patients were treated within 7 days of the previous event, sometimes within 24 hours.

Previous studies had shown that risk factors for poor outcomes included stenting within 10 days of the last event, stenting a posterior circulation target lesion, stenting presentations other than stroke, and sites with a low patient volume for stenting. Patient selection is vital to success, according to Dr. Alexander. Patients with hemodynamic compromise are good candidates for stenting, while those with perforator stroke alone are better off with medical therapy. Embolic stroke patients are candidates for either approach.

WEAVE looked at 152 consecutive patients treated on label at 24 institutions. The primary analysis group consisted of patients with a 70%-99% stenotic intracranial atherosclerotic lesion who were refractory to medical treatment, 22-80 years of age, and had a modified Rankin Scale (mRS) score of 3 or less at baseline. The treatment was performed at least 7 days after the last stroke. Finally, patients had to have experienced two or more strokes. This last requirement presented a problem for recruitment, according to Dr. Alexander. “That was never a criterion for any of the [previous] trials, so it’s not clear why FDA added that. That made it very difficult to enroll for this trial – to have patients who had two or more strokes and still had a functional mRS score,” he said.

The study protocol aimed for a frequency of 6.6% for periprocedural morbidity, defined as a stroke or death within 72 hours.

An interim analysis at 100 patients showed that the periprocedural morbidity frequency was below 4%, which met the agency’s requirement and allowed the trial to be halted once the trial enrolled 150 on-label patients. The total number of on-label patients reached 152, and the researchers analyzed the results from another 46 patients who were treated with stenting despite not meeting the study’s inclusion criteria, and these patients were considered to be off-label use. The final analysis showed that the on-label group had a periprocedural morbidity of 2.6%, compared with 23.9% in the off-label group (P = .0001).

The most glaring difference in the patient populations was that half of the off-label group received the stent within 7 days of experiencing a stroke. What might be the reason for worse outcomes when stenting is performed within 7 days? “There’s speculation that the plaques might be hot, and those patients might have a higher thrombotic risk with putting a foreign body in the vessel, or there’s capillary instability, so reperfusing a vessel that has a 99% stenosis has a higher risk for reperfusion hemorrhage,” Dr. Alexander said.

Experience may also be a factor. Interventionalists participating in the WEAVE trial had performed a stent using Wingspan an average of 37 times before the study began, compared with a mean of 10 cases for physicians in the SAMMPRIS trial. Those who had performed over 50 procedures had no periprocedural morbidity outcomes at all.

The study was funded by Stryker Neurovascular. Dr. Alexander has consulted for Stryker.

SOURCE: Alexander M et al. ISC 2018 Abstract LB13.

Open inguinal hernia repair with lightweight mesh resulted in a lower-level sensation of groin lump and less discomfort at 1 year in a group of patients who had lightweight mesh, compared with patients who had heavyweight mesh, in a multicenter, randomized clinical trial.

Martin Rutegård, MD, of Umeå (Sweden) University, and his research associates reported that 3%-10% of all hernia surgeries “result in severe or moderately severe pain for more than a year after hernia surgery, which may have a significant impact on social activities, sex life, and quality of life. ... Interest in the use of lightweight meshes in groin hernia repair has increased in recent years, as it is assumed that this type of mesh may cause less discomfort and chronic pain.”

castillodominici/Thinkstock

[email protected]

SOURCE: M. Rutegård et al. Hernia 2018 Jan 20. doi: 10.1007/s10029-018-1734-z.

Open inguinal hernia repair with lightweight mesh resulted in a lower-level sensation of groin lump and less discomfort at 1 year in a group of patients who had lightweight mesh, compared with patients who had heavyweight mesh, in a multicenter, randomized clinical trial.

Martin Rutegård, MD, of Umeå (Sweden) University, and his research associates reported that 3%-10% of all hernia surgeries “result in severe or moderately severe pain for more than a year after hernia surgery, which may have a significant impact on social activities, sex life, and quality of life. ... Interest in the use of lightweight meshes in groin hernia repair has increased in recent years, as it is assumed that this type of mesh may cause less discomfort and chronic pain.”

castillodominici/Thinkstock

[email protected]

SOURCE: M. Rutegård et al. Hernia 2018 Jan 20. doi: 10.1007/s10029-018-1734-z.

Open inguinal hernia repair with lightweight mesh resulted in a lower-level sensation of groin lump and less discomfort at 1 year in a group of patients who had lightweight mesh, compared with patients who had heavyweight mesh, in a multicenter, randomized clinical trial.

Martin Rutegård, MD, of Umeå (Sweden) University, and his research associates reported that 3%-10% of all hernia surgeries “result in severe or moderately severe pain for more than a year after hernia surgery, which may have a significant impact on social activities, sex life, and quality of life. ... Interest in the use of lightweight meshes in groin hernia repair has increased in recent years, as it is assumed that this type of mesh may cause less discomfort and chronic pain.”

castillodominici/Thinkstock

[email protected]

SOURCE: M. Rutegård et al. Hernia 2018 Jan 20. doi: 10.1007/s10029-018-1734-z.

KAUAI, HAWAII – When someone reacts to a tixocortol pivalate skin patch, it doesn’t necessarily mean that topical steroids are no longer a treatment option.

That’s sometimes the assumption, but it’s incorrect, according to Mark Davis, MD, chair of the department of dermatology at the Mayo Clinic, Rochester, Minn. Tixocortol is the marker for topical steroid allergy in many series of patch tests, but there is research showing that it is a marker for one class of topical steroids, and “there’s substantial literature saying that if you’re only reacting to tixocortol pivalate, it should be safe to use other classes of topical steroids,” he said.

It’s also important to remember that skin patch tests need to be checked on day 5, not just day 3; it’s the only way to differentiate a true skin allergy from mere skin irritation, and it does matter.

Dr. Davis explained those issues and more – including what to do with minor reactions and how to use the T.R.U.E. TEST kit – in an interview filled with pearls at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Meanwhile, during a presentation at the meeting, he noted two newer options to help allergic patients find skin care products they won’t react to: the Mayo Clinic’s SkinSAFE database and the Contact Allergen Management Program from the American Contact Dermatitis Society.

Dr. Davis had no disclosures.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

KAUAI, HAWAII – When someone reacts to a tixocortol pivalate skin patch, it doesn’t necessarily mean that topical steroids are no longer a treatment option.

That’s sometimes the assumption, but it’s incorrect, according to Mark Davis, MD, chair of the department of dermatology at the Mayo Clinic, Rochester, Minn. Tixocortol is the marker for topical steroid allergy in many series of patch tests, but there is research showing that it is a marker for one class of topical steroids, and “there’s substantial literature saying that if you’re only reacting to tixocortol pivalate, it should be safe to use other classes of topical steroids,” he said.

It’s also important to remember that skin patch tests need to be checked on day 5, not just day 3; it’s the only way to differentiate a true skin allergy from mere skin irritation, and it does matter.

Dr. Davis explained those issues and more – including what to do with minor reactions and how to use the T.R.U.E. TEST kit – in an interview filled with pearls at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Meanwhile, during a presentation at the meeting, he noted two newer options to help allergic patients find skin care products they won’t react to: the Mayo Clinic’s SkinSAFE database and the Contact Allergen Management Program from the American Contact Dermatitis Society.

Dr. Davis had no disclosures.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

KAUAI, HAWAII – When someone reacts to a tixocortol pivalate skin patch, it doesn’t necessarily mean that topical steroids are no longer a treatment option.

That’s sometimes the assumption, but it’s incorrect, according to Mark Davis, MD, chair of the department of dermatology at the Mayo Clinic, Rochester, Minn. Tixocortol is the marker for topical steroid allergy in many series of patch tests, but there is research showing that it is a marker for one class of topical steroids, and “there’s substantial literature saying that if you’re only reacting to tixocortol pivalate, it should be safe to use other classes of topical steroids,” he said.

It’s also important to remember that skin patch tests need to be checked on day 5, not just day 3; it’s the only way to differentiate a true skin allergy from mere skin irritation, and it does matter.

Dr. Davis explained those issues and more – including what to do with minor reactions and how to use the T.R.U.E. TEST kit – in an interview filled with pearls at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Meanwhile, during a presentation at the meeting, he noted two newer options to help allergic patients find skin care products they won’t react to: the Mayo Clinic’s SkinSAFE database and the Contact Allergen Management Program from the American Contact Dermatitis Society.

Dr. Davis had no disclosures.

SDEF/Global Academy for Medical Education and this news organization are owned by the same parent company.

[email protected]

SAN DIEGO – A new survey suggests that advanced practice providers who care for multiple sclerosis patients are highly satisfied with their jobs, which encompass a wide range of responsibilities.

Researchers received survey responses from 215 nurse practitioners and 395 physician assistants who answered Web questionnaires in 2016 and 2017. Of those who care for multiple sclerosis (MS) patients, 92.5% and 77.8% respectively said they provide at least 9 of 11 services, such as direct care, supportive services, and care coordination.

“Nurse practitioners in particular are providing lots of different services from diagnosis to education to symptom management,” said Michael T. Halpern, MD, PhD, MPH, of Temple University, Philadelphia. “Physician assistants are also providing a diverse range of MS services, but not as frequently as nurse practitioners.”

Dr. Halpern was the presenting author of the study reporting the survey results. He spoke in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study findings were presented.

Advanced practice providers also reported high levels of job satisfaction. About 80% in both groups reported being very or extremely satisfied with their careers and with their colleagues; 90% of nurse practitioners reported being very or extremely satisfied by their relationships with patients, as did 86% of physician assistants.

The providers “appear to really enjoy working with individuals with MS,” Dr. Halpern said. But he cautioned that there’s a need for additional training for these providers; some respondents said their lack of knowledge was a hindrance to care.

The study was funded by the National Multiple Sclerosis Society. Dr. Halpern reported no relevant disclosures.

[email protected]

SAN DIEGO – A new survey suggests that advanced practice providers who care for multiple sclerosis patients are highly satisfied with their jobs, which encompass a wide range of responsibilities.

Researchers received survey responses from 215 nurse practitioners and 395 physician assistants who answered Web questionnaires in 2016 and 2017. Of those who care for multiple sclerosis (MS) patients, 92.5% and 77.8% respectively said they provide at least 9 of 11 services, such as direct care, supportive services, and care coordination.

“Nurse practitioners in particular are providing lots of different services from diagnosis to education to symptom management,” said Michael T. Halpern, MD, PhD, MPH, of Temple University, Philadelphia. “Physician assistants are also providing a diverse range of MS services, but not as frequently as nurse practitioners.”

Dr. Halpern was the presenting author of the study reporting the survey results. He spoke in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study findings were presented.

Advanced practice providers also reported high levels of job satisfaction. About 80% in both groups reported being very or extremely satisfied with their careers and with their colleagues; 90% of nurse practitioners reported being very or extremely satisfied by their relationships with patients, as did 86% of physician assistants.

The providers “appear to really enjoy working with individuals with MS,” Dr. Halpern said. But he cautioned that there’s a need for additional training for these providers; some respondents said their lack of knowledge was a hindrance to care.

The study was funded by the National Multiple Sclerosis Society. Dr. Halpern reported no relevant disclosures.

[email protected]

SAN DIEGO – A new survey suggests that advanced practice providers who care for multiple sclerosis patients are highly satisfied with their jobs, which encompass a wide range of responsibilities.

Researchers received survey responses from 215 nurse practitioners and 395 physician assistants who answered Web questionnaires in 2016 and 2017. Of those who care for multiple sclerosis (MS) patients, 92.5% and 77.8% respectively said they provide at least 9 of 11 services, such as direct care, supportive services, and care coordination.

“Nurse practitioners in particular are providing lots of different services from diagnosis to education to symptom management,” said Michael T. Halpern, MD, PhD, MPH, of Temple University, Philadelphia. “Physician assistants are also providing a diverse range of MS services, but not as frequently as nurse practitioners.”

Dr. Halpern was the presenting author of the study reporting the survey results. He spoke in a video interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, where the study findings were presented.

Advanced practice providers also reported high levels of job satisfaction. About 80% in both groups reported being very or extremely satisfied with their careers and with their colleagues; 90% of nurse practitioners reported being very or extremely satisfied by their relationships with patients, as did 86% of physician assistants.

The providers “appear to really enjoy working with individuals with MS,” Dr. Halpern said. But he cautioned that there’s a need for additional training for these providers; some respondents said their lack of knowledge was a hindrance to care.

The study was funded by the National Multiple Sclerosis Society. Dr. Halpern reported no relevant disclosures.

[email protected]

Ceftazidime-avibactam was noninferior to meropenem for nosocomial pneumonia including ventilator-associated pneumonia from gram-negative organisms, results from the REPROVE trial demonstrated.

Nosocomial or hospital-acquired pneumonia is a common hospital-acquired infection associated with increased cost and mortality. Further, nosocomial pneumonia is associated with gram-negative pathogens such as Pseudomonas aeruginosa and Enterobacteriaceae that may carry extended-spectrum beta-lactamases and carbapenemase, thereby limiting the treatment options. However, ceftazidime-avibactam has both antipseudomonal and extended beta-lactamase coverage for multidrug-resistant gram-negative infections, and may provide an alternative to meropenem.

copyright stockdevil/Thinkstock

Antoni Torres, MD, of the University of Barcelona and his colleagues sought to compare the safety and efficacy of ceftazidime-avibactam to meropenem in patients with nosocomial and ventilator-associated pneumonia. The REPROVE study was a phase 3, double-blind, noninferiority trial performed at 136 centers in 23 countries. Patients were randomly assigned 1:1 to receive either ceftazidime-avibactam (500-2,000 mg every 8 hours) or meropenem (1,000 mg every 8 hours) with adjustment as needed for renal function.

Participants included in the study were 18-90 years of age with nosocomial pneumonia as evidenced by pneumonia 48 hours or more after admission or within 7 days after discharge from an inpatient facility. Patients with ventilator-associated pneumonia had lung infection within 48 hours of intubation and mechanical ventilation. Sputum culture and gram stains were obtained within 48 hours before randomization, and patients were excluded for evidence of gram-positive–only pathogens or those not expected to respond to meropenem or ceftazidime-avibactam.

The study involved a safety population (808 patients), a clinically modified intention-to-treat population (726), and a clinically evaluable population (527). The intention-to-treat population demonstrated a predominance of Klebsiella pneumoniae (37%), and Pseudomonas aeruginosa (30%); 28% of the intention-to-treat population were identified as not susceptible to ceftazidime.

Overall, the clinically modified intention-to-treat group demonstrated a clinical cure rate of 68.8% (245/356) in the ceftazidime-avibactam and 73.0% (270/370) for the meropenem group (difference, –4.2%; 95% confidence interval, –10.8 to 2.5). The evaluable population demonstrated a clinical cure rate of 77.4% (199/257) in the ceftazidime-avibactam group and 78.1% (211/270) in the meropenem group (–0.7%; 95% CI, –7.9 to 6.4).

The all-cause mortality rate was similar between groups at the test-of-cure date and at day 28. The clinically modified intention-to-treat population demonstrated a mortality of 8.1% vs. 6.8% at the test-of-cure date and 8.4% vs. 7.3% at day 28 for ceftazidime-avibactam and meropenem, respectively.

Adverse events were noted in 75% vs. 74% of patients in the ceftazidime-avibactam groups and meropenem groups, respectively. Most adverse events were rated as mild to moderate and deemed likely unrelated to the treatment.

However, serious adverse events occurred in 19% (n = 75) in the ceftazidime-avibactam group and 13% (n = 54) in the meropenem group. Four serious adverse events were thought to be possibly related to the study drug ceftazidime-avibactam and included diarrhea, acute coronary syndrome, subacute hepatic failure, and abnormal liver function test results. The authors noted the adverse events in the trial were consistent and detected no new safety concerns for ceftazidime-avibactam.

Limitations of the study included an inability to establish the optimal duration of treatment for nosocomial pneumonia treated with meropenem or ceftazidime-avibactam.

“Our results show noninferiority for the treatment of nosocomial pneumonia caused by ceftazidime-nonsusceptible or ceftazidime-susceptible gram-negative aerobic pathogens,” the authors concluded.

The study was initially funded by AstraZeneca until the rights to ceftazidime-avibactam were acquired by Pfizer. Multiple authors reported financial relationships with AstraZeneca including grant funding, employment, and shareholding.
 

SOURCE: Torres A et al. Lancet Infect Dis. 2017. doi: 10.1016/S1473-3099(17)30747-8.

Ceftazidime-avibactam was noninferior to meropenem for nosocomial pneumonia including ventilator-associated pneumonia from gram-negative organisms, results from the REPROVE trial demonstrated.

Nosocomial or hospital-acquired pneumonia is a common hospital-acquired infection associated with increased cost and mortality. Further, nosocomial pneumonia is associated with gram-negative pathogens such as Pseudomonas aeruginosa and Enterobacteriaceae that may carry extended-spectrum beta-lactamases and carbapenemase, thereby limiting the treatment options. However, ceftazidime-avibactam has both antipseudomonal and extended beta-lactamase coverage for multidrug-resistant gram-negative infections, and may provide an alternative to meropenem.

copyright stockdevil/Thinkstock

Antoni Torres, MD, of the University of Barcelona and his colleagues sought to compare the safety and efficacy of ceftazidime-avibactam to meropenem in patients with nosocomial and ventilator-associated pneumonia. The REPROVE study was a phase 3, double-blind, noninferiority trial performed at 136 centers in 23 countries. Patients were randomly assigned 1:1 to receive either ceftazidime-avibactam (500-2,000 mg every 8 hours) or meropenem (1,000 mg every 8 hours) with adjustment as needed for renal function.

Participants included in the study were 18-90 years of age with nosocomial pneumonia as evidenced by pneumonia 48 hours or more after admission or within 7 days after discharge from an inpatient facility. Patients with ventilator-associated pneumonia had lung infection within 48 hours of intubation and mechanical ventilation. Sputum culture and gram stains were obtained within 48 hours before randomization, and patients were excluded for evidence of gram-positive–only pathogens or those not expected to respond to meropenem or ceftazidime-avibactam.

The study involved a safety population (808 patients), a clinically modified intention-to-treat population (726), and a clinically evaluable population (527). The intention-to-treat population demonstrated a predominance of Klebsiella pneumoniae (37%), and Pseudomonas aeruginosa (30%); 28% of the intention-to-treat population were identified as not susceptible to ceftazidime.

Overall, the clinically modified intention-to-treat group demonstrated a clinical cure rate of 68.8% (245/356) in the ceftazidime-avibactam and 73.0% (270/370) for the meropenem group (difference, –4.2%; 95% confidence interval, –10.8 to 2.5). The evaluable population demonstrated a clinical cure rate of 77.4% (199/257) in the ceftazidime-avibactam group and 78.1% (211/270) in the meropenem group (–0.7%; 95% CI, –7.9 to 6.4).

The all-cause mortality rate was similar between groups at the test-of-cure date and at day 28. The clinically modified intention-to-treat population demonstrated a mortality of 8.1% vs. 6.8% at the test-of-cure date and 8.4% vs. 7.3% at day 28 for ceftazidime-avibactam and meropenem, respectively.

Adverse events were noted in 75% vs. 74% of patients in the ceftazidime-avibactam groups and meropenem groups, respectively. Most adverse events were rated as mild to moderate and deemed likely unrelated to the treatment.

However, serious adverse events occurred in 19% (n = 75) in the ceftazidime-avibactam group and 13% (n = 54) in the meropenem group. Four serious adverse events were thought to be possibly related to the study drug ceftazidime-avibactam and included diarrhea, acute coronary syndrome, subacute hepatic failure, and abnormal liver function test results. The authors noted the adverse events in the trial were consistent and detected no new safety concerns for ceftazidime-avibactam.

Limitations of the study included an inability to establish the optimal duration of treatment for nosocomial pneumonia treated with meropenem or ceftazidime-avibactam.

“Our results show noninferiority for the treatment of nosocomial pneumonia caused by ceftazidime-nonsusceptible or ceftazidime-susceptible gram-negative aerobic pathogens,” the authors concluded.

The study was initially funded by AstraZeneca until the rights to ceftazidime-avibactam were acquired by Pfizer. Multiple authors reported financial relationships with AstraZeneca including grant funding, employment, and shareholding.
 

SOURCE: Torres A et al. Lancet Infect Dis. 2017. doi: 10.1016/S1473-3099(17)30747-8.

Ceftazidime-avibactam was noninferior to meropenem for nosocomial pneumonia including ventilator-associated pneumonia from gram-negative organisms, results from the REPROVE trial demonstrated.

Nosocomial or hospital-acquired pneumonia is a common hospital-acquired infection associated with increased cost and mortality. Further, nosocomial pneumonia is associated with gram-negative pathogens such as Pseudomonas aeruginosa and Enterobacteriaceae that may carry extended-spectrum beta-lactamases and carbapenemase, thereby limiting the treatment options. However, ceftazidime-avibactam has both antipseudomonal and extended beta-lactamase coverage for multidrug-resistant gram-negative infections, and may provide an alternative to meropenem.

copyright stockdevil/Thinkstock

Antoni Torres, MD, of the University of Barcelona and his colleagues sought to compare the safety and efficacy of ceftazidime-avibactam to meropenem in patients with nosocomial and ventilator-associated pneumonia. The REPROVE study was a phase 3, double-blind, noninferiority trial performed at 136 centers in 23 countries. Patients were randomly assigned 1:1 to receive either ceftazidime-avibactam (500-2,000 mg every 8 hours) or meropenem (1,000 mg every 8 hours) with adjustment as needed for renal function.

Participants included in the study were 18-90 years of age with nosocomial pneumonia as evidenced by pneumonia 48 hours or more after admission or within 7 days after discharge from an inpatient facility. Patients with ventilator-associated pneumonia had lung infection within 48 hours of intubation and mechanical ventilation. Sputum culture and gram stains were obtained within 48 hours before randomization, and patients were excluded for evidence of gram-positive–only pathogens or those not expected to respond to meropenem or ceftazidime-avibactam.

The study involved a safety population (808 patients), a clinically modified intention-to-treat population (726), and a clinically evaluable population (527). The intention-to-treat population demonstrated a predominance of Klebsiella pneumoniae (37%), and Pseudomonas aeruginosa (30%); 28% of the intention-to-treat population were identified as not susceptible to ceftazidime.

Overall, the clinically modified intention-to-treat group demonstrated a clinical cure rate of 68.8% (245/356) in the ceftazidime-avibactam and 73.0% (270/370) for the meropenem group (difference, –4.2%; 95% confidence interval, –10.8 to 2.5). The evaluable population demonstrated a clinical cure rate of 77.4% (199/257) in the ceftazidime-avibactam group and 78.1% (211/270) in the meropenem group (–0.7%; 95% CI, –7.9 to 6.4).

The all-cause mortality rate was similar between groups at the test-of-cure date and at day 28. The clinically modified intention-to-treat population demonstrated a mortality of 8.1% vs. 6.8% at the test-of-cure date and 8.4% vs. 7.3% at day 28 for ceftazidime-avibactam and meropenem, respectively.

Adverse events were noted in 75% vs. 74% of patients in the ceftazidime-avibactam groups and meropenem groups, respectively. Most adverse events were rated as mild to moderate and deemed likely unrelated to the treatment.

However, serious adverse events occurred in 19% (n = 75) in the ceftazidime-avibactam group and 13% (n = 54) in the meropenem group. Four serious adverse events were thought to be possibly related to the study drug ceftazidime-avibactam and included diarrhea, acute coronary syndrome, subacute hepatic failure, and abnormal liver function test results. The authors noted the adverse events in the trial were consistent and detected no new safety concerns for ceftazidime-avibactam.

Limitations of the study included an inability to establish the optimal duration of treatment for nosocomial pneumonia treated with meropenem or ceftazidime-avibactam.

“Our results show noninferiority for the treatment of nosocomial pneumonia caused by ceftazidime-nonsusceptible or ceftazidime-susceptible gram-negative aerobic pathogens,” the authors concluded.

The study was initially funded by AstraZeneca until the rights to ceftazidime-avibactam were acquired by Pfizer. Multiple authors reported financial relationships with AstraZeneca including grant funding, employment, and shareholding.
 

SOURCE: Torres A et al. Lancet Infect Dis. 2017. doi: 10.1016/S1473-3099(17)30747-8.

SAN DIEGO – Delayed-release dimethyl fumarate did not show any differences versus fingolimod in relapse rate over a 1-year, “real-world” study of patients with relapsing-remitting multiple sclerosis, but a significantly greater proportion of patients taking delayed-release dimethyl fumarate achieved relapse-free status and a lower annualized relapsed rate, compared with patients on glatiramer acetate

“There is a need for real-world data that compares the effectiveness of the growing number of MS [multiple sclerosis] treatment options,” Christophe Hotermans, MD, vice president of Global Medical Therapeutic Areas at Boston-based Biogen, said in an interview during ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “These results were consistent with previous analyses of efficacy of these treatments in people with relapsing-remitting MS, which showed no significant differences in efficacy between delayed-release dimethyl fumarate [DMF, Tecfidera] versus fingolimod [FTY, Gilenya] and greater efficacy with dimethyl fumarate, compared with glatiramer acetate [GA].”

The findings come from EFFECT (Observational Study to Characterize Real-world Clinical Outcomes With Relapsing-remitting Multiple Sclerosis), a multicenter, international, retrospective, single-time-point medical record review study comparing the effectiveness of DMF vs. other disease-modifying therapies, including FTY and GA in patients with relapsing-remitting MS.

Endpoints included the Kaplan-Meier estimated proportion of patients who relapsed at 12 months and annualized relapse rate. Baseline covariates were used in estimating propensity scores. The data were divided into four strata using quartiles of propensity scores. After assessing for balance in baseline covariates between the treatment groups, Kaplan-Meier estimates of relapse and estimates of treatment effects were pooled across the four strata.

At the meeting, Jinny Min, PharmD, a medical postdoctoral research fellow at Biogen, reported results from 816 DMF patients, 781 FTY patients, and 1,042 GA patients. In the trimmed analysis set, the estimated proportion of DMF and FTY patients who relapsed at 12 months after treatment initiation was 12% vs. 13%, respectively (hazard ratio, 1.07, P = .693; the adjusted rate ratio for annualized relapse was 1.09, P = .617). In the analysis of DMF vs. GA patients, the estimated proportion of DMF patients that relapsed at 12 months was 12% vs. 21%, respectively (HR, 0.71), which represented a significant decrease of 29% (P less than .02). The adjusted rate ratio for annualized relapse was 0.69, representing a significant decrease of 31% (P less than .01).

“We hope that these data help health care providers and people living with MS as they consider their treatment options,” Dr. Hotermans said. “The limitations of this study are similar to those that would be present in other retrospective studies that utilize real-world data. However, we worked to mitigate many of those limitations through a propensity-score estimation approach to adjust for confounders. An additional limitation that is inherent to the study design (retrospective chart review) is that patients’ medical history, MS disease, treatment history, and relapse history were limited to the information available in the medical records.”

The study was supported by Biogen, which markets DMF. Dr. Hotermans and Dr. Min are employees of the company.

[email protected]

SOURCE: Min J et al. ACTRIMS Forum 2018, Abstract P016.

SAN DIEGO – Delayed-release dimethyl fumarate did not show any differences versus fingolimod in relapse rate over a 1-year, “real-world” study of patients with relapsing-remitting multiple sclerosis, but a significantly greater proportion of patients taking delayed-release dimethyl fumarate achieved relapse-free status and a lower annualized relapsed rate, compared with patients on glatiramer acetate

“There is a need for real-world data that compares the effectiveness of the growing number of MS [multiple sclerosis] treatment options,” Christophe Hotermans, MD, vice president of Global Medical Therapeutic Areas at Boston-based Biogen, said in an interview during ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “These results were consistent with previous analyses of efficacy of these treatments in people with relapsing-remitting MS, which showed no significant differences in efficacy between delayed-release dimethyl fumarate [DMF, Tecfidera] versus fingolimod [FTY, Gilenya] and greater efficacy with dimethyl fumarate, compared with glatiramer acetate [GA].”

The findings come from EFFECT (Observational Study to Characterize Real-world Clinical Outcomes With Relapsing-remitting Multiple Sclerosis), a multicenter, international, retrospective, single-time-point medical record review study comparing the effectiveness of DMF vs. other disease-modifying therapies, including FTY and GA in patients with relapsing-remitting MS.

Endpoints included the Kaplan-Meier estimated proportion of patients who relapsed at 12 months and annualized relapse rate. Baseline covariates were used in estimating propensity scores. The data were divided into four strata using quartiles of propensity scores. After assessing for balance in baseline covariates between the treatment groups, Kaplan-Meier estimates of relapse and estimates of treatment effects were pooled across the four strata.

At the meeting, Jinny Min, PharmD, a medical postdoctoral research fellow at Biogen, reported results from 816 DMF patients, 781 FTY patients, and 1,042 GA patients. In the trimmed analysis set, the estimated proportion of DMF and FTY patients who relapsed at 12 months after treatment initiation was 12% vs. 13%, respectively (hazard ratio, 1.07, P = .693; the adjusted rate ratio for annualized relapse was 1.09, P = .617). In the analysis of DMF vs. GA patients, the estimated proportion of DMF patients that relapsed at 12 months was 12% vs. 21%, respectively (HR, 0.71), which represented a significant decrease of 29% (P less than .02). The adjusted rate ratio for annualized relapse was 0.69, representing a significant decrease of 31% (P less than .01).

“We hope that these data help health care providers and people living with MS as they consider their treatment options,” Dr. Hotermans said. “The limitations of this study are similar to those that would be present in other retrospective studies that utilize real-world data. However, we worked to mitigate many of those limitations through a propensity-score estimation approach to adjust for confounders. An additional limitation that is inherent to the study design (retrospective chart review) is that patients’ medical history, MS disease, treatment history, and relapse history were limited to the information available in the medical records.”

The study was supported by Biogen, which markets DMF. Dr. Hotermans and Dr. Min are employees of the company.

[email protected]

SOURCE: Min J et al. ACTRIMS Forum 2018, Abstract P016.

SAN DIEGO – Delayed-release dimethyl fumarate did not show any differences versus fingolimod in relapse rate over a 1-year, “real-world” study of patients with relapsing-remitting multiple sclerosis, but a significantly greater proportion of patients taking delayed-release dimethyl fumarate achieved relapse-free status and a lower annualized relapsed rate, compared with patients on glatiramer acetate

“There is a need for real-world data that compares the effectiveness of the growing number of MS [multiple sclerosis] treatment options,” Christophe Hotermans, MD, vice president of Global Medical Therapeutic Areas at Boston-based Biogen, said in an interview during ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “These results were consistent with previous analyses of efficacy of these treatments in people with relapsing-remitting MS, which showed no significant differences in efficacy between delayed-release dimethyl fumarate [DMF, Tecfidera] versus fingolimod [FTY, Gilenya] and greater efficacy with dimethyl fumarate, compared with glatiramer acetate [GA].”

The findings come from EFFECT (Observational Study to Characterize Real-world Clinical Outcomes With Relapsing-remitting Multiple Sclerosis), a multicenter, international, retrospective, single-time-point medical record review study comparing the effectiveness of DMF vs. other disease-modifying therapies, including FTY and GA in patients with relapsing-remitting MS.

Endpoints included the Kaplan-Meier estimated proportion of patients who relapsed at 12 months and annualized relapse rate. Baseline covariates were used in estimating propensity scores. The data were divided into four strata using quartiles of propensity scores. After assessing for balance in baseline covariates between the treatment groups, Kaplan-Meier estimates of relapse and estimates of treatment effects were pooled across the four strata.

At the meeting, Jinny Min, PharmD, a medical postdoctoral research fellow at Biogen, reported results from 816 DMF patients, 781 FTY patients, and 1,042 GA patients. In the trimmed analysis set, the estimated proportion of DMF and FTY patients who relapsed at 12 months after treatment initiation was 12% vs. 13%, respectively (hazard ratio, 1.07, P = .693; the adjusted rate ratio for annualized relapse was 1.09, P = .617). In the analysis of DMF vs. GA patients, the estimated proportion of DMF patients that relapsed at 12 months was 12% vs. 21%, respectively (HR, 0.71), which represented a significant decrease of 29% (P less than .02). The adjusted rate ratio for annualized relapse was 0.69, representing a significant decrease of 31% (P less than .01).

“We hope that these data help health care providers and people living with MS as they consider their treatment options,” Dr. Hotermans said. “The limitations of this study are similar to those that would be present in other retrospective studies that utilize real-world data. However, we worked to mitigate many of those limitations through a propensity-score estimation approach to adjust for confounders. An additional limitation that is inherent to the study design (retrospective chart review) is that patients’ medical history, MS disease, treatment history, and relapse history were limited to the information available in the medical records.”

The study was supported by Biogen, which markets DMF. Dr. Hotermans and Dr. Min are employees of the company.

[email protected]

SOURCE: Min J et al. ACTRIMS Forum 2018, Abstract P016.

Nearly 10% of children with systemic lupus erythematosus (SLE) developed macrophage activation syndrome (MAS) at some point during a mean follow-up time of more than 3 years at one center, and most were concomitantly diagnosed with the syndrome.

Although the investigators from the University of Toronto reported significantly higher mortality among patients with MAS, most cases were successfully treated with corticosteroids, and no relapses were observed during follow-up.

MAS was first identified in patients with juvenile idiopathic arthritis and is most well known as a complication of that broadly named disease, but data on outcomes and disease course in SLE patients are limited, first author Roberto Ezequiel Borgia, MD, and his colleagues wrote in their report in Arthritis & Rheumatology.

The researchers identified 403 children with SLE seen at the Hospital for Sick Children in Toronto during 2002-2012. Overall, 38 patients (9%) had MAS; of those patients, 68% received a MAS diagnosis within 7 days of the SLE diagnosis – termed “concomitant” diagnosis – while another 29% received a MAS diagnosis within 180 days of their SLE diagnosis.

The researchers explained that “since there are no validated nor universally accepted diagnostic criteria for MAS in SLE, the definition of MAS was based on the treating pediatric rheumatologist’s expert opinion at the time of the initial presentation.” The most common presenting feature of MAS was fever (100%), followed by generalized lymphadenopathy (24%), hepatomegaly (18%), CNS dysfunction secondary to MAS (18%), hemorrhage (13%), and splenomegaly (10%).

The average age of the children at diagnosis was nearly 14 years, and 79% were female. The average follow-up was 3.5 years. There were no significant differences in the demographic features of children with and without MAS nor were there any in variables used to assess lupus outcomes, which included immunosuppressive drug use, average daily corticosteroid dose (18.3 mg/day with MAS vs. 18.6 mg/day without MAS), and the number of pediatric ICU visits (incidence rate ratio for MAS vs. non-MAS, 1.60 [95% CI, 0.74-3.18]).

Mortality was significantly higher in children with MAS, compared with those without MAS (5.3% vs. 0.3%; P = .02), although the overall number of deaths in the cohort was small (n = 3). Apart from the “acute illness which was associated with 2 deaths secondary to MAS,” the investigators said that they “did not find any significant differences in the number of deaths or damage accrual between the cohorts, including overall SLICC [Systemic Lupus International Collaborating Clinics] damage score or any specific damage feature within the score.”

The study findings were limited by several factors including the lack of validated MAS criteria for children with SLE and a lack of follow-up data on the patients beyond 18 years of age, the researchers said.

The results suggest that MAS remains a life-threatening complication in children with SLE and should be considered an important cause of mortality for them, but “if the initial presentation does not result in death, the long-term outcome seem[s] to be comparable to those without MAS,” the investigators wrote.

The researchers had no financial conflicts to disclose.

[email protected]

SOURCE: Borgia R et al. Arthritis Rheumatol. 2018 Jan 17. doi: 10.1002/art.40417

Nearly 10% of children with systemic lupus erythematosus (SLE) developed macrophage activation syndrome (MAS) at some point during a mean follow-up time of more than 3 years at one center, and most were concomitantly diagnosed with the syndrome.

Although the investigators from the University of Toronto reported significantly higher mortality among patients with MAS, most cases were successfully treated with corticosteroids, and no relapses were observed during follow-up.

MAS was first identified in patients with juvenile idiopathic arthritis and is most well known as a complication of that broadly named disease, but data on outcomes and disease course in SLE patients are limited, first author Roberto Ezequiel Borgia, MD, and his colleagues wrote in their report in Arthritis & Rheumatology.

The researchers identified 403 children with SLE seen at the Hospital for Sick Children in Toronto during 2002-2012. Overall, 38 patients (9%) had MAS; of those patients, 68% received a MAS diagnosis within 7 days of the SLE diagnosis – termed “concomitant” diagnosis – while another 29% received a MAS diagnosis within 180 days of their SLE diagnosis.

The researchers explained that “since there are no validated nor universally accepted diagnostic criteria for MAS in SLE, the definition of MAS was based on the treating pediatric rheumatologist’s expert opinion at the time of the initial presentation.” The most common presenting feature of MAS was fever (100%), followed by generalized lymphadenopathy (24%), hepatomegaly (18%), CNS dysfunction secondary to MAS (18%), hemorrhage (13%), and splenomegaly (10%).

The average age of the children at diagnosis was nearly 14 years, and 79% were female. The average follow-up was 3.5 years. There were no significant differences in the demographic features of children with and without MAS nor were there any in variables used to assess lupus outcomes, which included immunosuppressive drug use, average daily corticosteroid dose (18.3 mg/day with MAS vs. 18.6 mg/day without MAS), and the number of pediatric ICU visits (incidence rate ratio for MAS vs. non-MAS, 1.60 [95% CI, 0.74-3.18]).

Mortality was significantly higher in children with MAS, compared with those without MAS (5.3% vs. 0.3%; P = .02), although the overall number of deaths in the cohort was small (n = 3). Apart from the “acute illness which was associated with 2 deaths secondary to MAS,” the investigators said that they “did not find any significant differences in the number of deaths or damage accrual between the cohorts, including overall SLICC [Systemic Lupus International Collaborating Clinics] damage score or any specific damage feature within the score.”

The study findings were limited by several factors including the lack of validated MAS criteria for children with SLE and a lack of follow-up data on the patients beyond 18 years of age, the researchers said.

The results suggest that MAS remains a life-threatening complication in children with SLE and should be considered an important cause of mortality for them, but “if the initial presentation does not result in death, the long-term outcome seem[s] to be comparable to those without MAS,” the investigators wrote.

The researchers had no financial conflicts to disclose.

[email protected]

SOURCE: Borgia R et al. Arthritis Rheumatol. 2018 Jan 17. doi: 10.1002/art.40417

Nearly 10% of children with systemic lupus erythematosus (SLE) developed macrophage activation syndrome (MAS) at some point during a mean follow-up time of more than 3 years at one center, and most were concomitantly diagnosed with the syndrome.

Although the investigators from the University of Toronto reported significantly higher mortality among patients with MAS, most cases were successfully treated with corticosteroids, and no relapses were observed during follow-up.

MAS was first identified in patients with juvenile idiopathic arthritis and is most well known as a complication of that broadly named disease, but data on outcomes and disease course in SLE patients are limited, first author Roberto Ezequiel Borgia, MD, and his colleagues wrote in their report in Arthritis & Rheumatology.

The researchers identified 403 children with SLE seen at the Hospital for Sick Children in Toronto during 2002-2012. Overall, 38 patients (9%) had MAS; of those patients, 68% received a MAS diagnosis within 7 days of the SLE diagnosis – termed “concomitant” diagnosis – while another 29% received a MAS diagnosis within 180 days of their SLE diagnosis.

The researchers explained that “since there are no validated nor universally accepted diagnostic criteria for MAS in SLE, the definition of MAS was based on the treating pediatric rheumatologist’s expert opinion at the time of the initial presentation.” The most common presenting feature of MAS was fever (100%), followed by generalized lymphadenopathy (24%), hepatomegaly (18%), CNS dysfunction secondary to MAS (18%), hemorrhage (13%), and splenomegaly (10%).

The average age of the children at diagnosis was nearly 14 years, and 79% were female. The average follow-up was 3.5 years. There were no significant differences in the demographic features of children with and without MAS nor were there any in variables used to assess lupus outcomes, which included immunosuppressive drug use, average daily corticosteroid dose (18.3 mg/day with MAS vs. 18.6 mg/day without MAS), and the number of pediatric ICU visits (incidence rate ratio for MAS vs. non-MAS, 1.60 [95% CI, 0.74-3.18]).

Mortality was significantly higher in children with MAS, compared with those without MAS (5.3% vs. 0.3%; P = .02), although the overall number of deaths in the cohort was small (n = 3). Apart from the “acute illness which was associated with 2 deaths secondary to MAS,” the investigators said that they “did not find any significant differences in the number of deaths or damage accrual between the cohorts, including overall SLICC [Systemic Lupus International Collaborating Clinics] damage score or any specific damage feature within the score.”

The study findings were limited by several factors including the lack of validated MAS criteria for children with SLE and a lack of follow-up data on the patients beyond 18 years of age, the researchers said.

The results suggest that MAS remains a life-threatening complication in children with SLE and should be considered an important cause of mortality for them, but “if the initial presentation does not result in death, the long-term outcome seem[s] to be comparable to those without MAS,” the investigators wrote.

The researchers had no financial conflicts to disclose.

[email protected]

SOURCE: Borgia R et al. Arthritis Rheumatol. 2018 Jan 17. doi: 10.1002/art.40417