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Microsensor perfectly distinguished coagulopathy patients from controls
SAN DIEGO – Using less than a drop of blood, a portable microsensor provided a comprehensive coagulation profile in less than 15 minutes and perfectly distinguished various coagulopathies from normal blood samples – handily beating the results with both activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Dubbed ClotChip, the disposable device detects coagulation factors and platelet activity using dielectric spectroscopy, Evi X. Stavrou, MD, said at the annual meeting of the American Society of Hematology. The development points the way for comprehensive, rapid, point-of-care assessment of critically ill or severely injured patients and those who need ongoing monitoring to evaluate response to anticoagulant therapy, she added.
Existing point-of-care coagulation assays have several shortcomings, Dr. Stavrou, of Case Western Reserve University, Cleveland, said during a press briefing at the conference. They are relatively insensitive, fail to measure platelet activity, or are only approved for specific subgroups of patients, such as those on warfarin, she specified.
To develop an alternative, Dr. Stavrou and her associates added a parallel-plate capacitive sensing structure to an inexpensive, disposable microfluidic biochip designed to test 9 microliters (less than one drop) of blood. They built the microsensor from biocompatible and chemically inert materials to minimize the chances of artificial contact activation.
To test the device, the researchers used calcium dichloride to induce coagulation in whole blood samples from 11 controls with normal aPTT and PT values. Time curves of output from the microsensor showed that coagulation consistently peaked within 4.5 to 6 minutes.
Next, the investigators tested blood from 12 patients with coagulopathies, including hemophilia A, hemophilia B, acquired von Willebrand factor defect, and congenital hypodysfibrinogenemia. These samples all yielded abnormal curves, with prolonged times to peak that ranged between 7 and 15 minutes – significantly exceeding those of healthy controls (P = .0002).
By plotting rates of true positives against rates of true negatives, the researchers obtained areas under the receiver operating curves of 100% for ClotChip, 78% for aPTT, and 57% for PT. In other words, ClotChip correctly identified all cases and controls in this small patient cohort, which neither aPTT or PT did.
Finally, the researchers used the microsensor to measure coagulation activity in normal blood samples that they treated with prostaglandin E2 to inhibit platelet aggregation. Normalized permittivity (an electrical measure) was significantly lower than in untreated control samples (P = .03), but time to peak values were the same in both groups. This finding confirms that the chip can identify abnormal platelet function, Dr. Stavrou said. “ClotChip is sensitive to the complete hemostasis process, exhibits better sensitivity and specificity than conventional coagulation assays, and discriminates between coagulation and platelet defects,” she concluded.
The investigators are recruiting volunteers for an expanded round of testing for the device, and are working to optimize construction to further enhance its sensitivity.
Dr. Stavrou and her coinvestigators had no relevant financial disclosures.
SAN DIEGO – Using less than a drop of blood, a portable microsensor provided a comprehensive coagulation profile in less than 15 minutes and perfectly distinguished various coagulopathies from normal blood samples – handily beating the results with both activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Dubbed ClotChip, the disposable device detects coagulation factors and platelet activity using dielectric spectroscopy, Evi X. Stavrou, MD, said at the annual meeting of the American Society of Hematology. The development points the way for comprehensive, rapid, point-of-care assessment of critically ill or severely injured patients and those who need ongoing monitoring to evaluate response to anticoagulant therapy, she added.
Existing point-of-care coagulation assays have several shortcomings, Dr. Stavrou, of Case Western Reserve University, Cleveland, said during a press briefing at the conference. They are relatively insensitive, fail to measure platelet activity, or are only approved for specific subgroups of patients, such as those on warfarin, she specified.
To develop an alternative, Dr. Stavrou and her associates added a parallel-plate capacitive sensing structure to an inexpensive, disposable microfluidic biochip designed to test 9 microliters (less than one drop) of blood. They built the microsensor from biocompatible and chemically inert materials to minimize the chances of artificial contact activation.
To test the device, the researchers used calcium dichloride to induce coagulation in whole blood samples from 11 controls with normal aPTT and PT values. Time curves of output from the microsensor showed that coagulation consistently peaked within 4.5 to 6 minutes.
Next, the investigators tested blood from 12 patients with coagulopathies, including hemophilia A, hemophilia B, acquired von Willebrand factor defect, and congenital hypodysfibrinogenemia. These samples all yielded abnormal curves, with prolonged times to peak that ranged between 7 and 15 minutes – significantly exceeding those of healthy controls (P = .0002).
By plotting rates of true positives against rates of true negatives, the researchers obtained areas under the receiver operating curves of 100% for ClotChip, 78% for aPTT, and 57% for PT. In other words, ClotChip correctly identified all cases and controls in this small patient cohort, which neither aPTT or PT did.
Finally, the researchers used the microsensor to measure coagulation activity in normal blood samples that they treated with prostaglandin E2 to inhibit platelet aggregation. Normalized permittivity (an electrical measure) was significantly lower than in untreated control samples (P = .03), but time to peak values were the same in both groups. This finding confirms that the chip can identify abnormal platelet function, Dr. Stavrou said. “ClotChip is sensitive to the complete hemostasis process, exhibits better sensitivity and specificity than conventional coagulation assays, and discriminates between coagulation and platelet defects,” she concluded.
The investigators are recruiting volunteers for an expanded round of testing for the device, and are working to optimize construction to further enhance its sensitivity.
Dr. Stavrou and her coinvestigators had no relevant financial disclosures.
SAN DIEGO – Using less than a drop of blood, a portable microsensor provided a comprehensive coagulation profile in less than 15 minutes and perfectly distinguished various coagulopathies from normal blood samples – handily beating the results with both activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Dubbed ClotChip, the disposable device detects coagulation factors and platelet activity using dielectric spectroscopy, Evi X. Stavrou, MD, said at the annual meeting of the American Society of Hematology. The development points the way for comprehensive, rapid, point-of-care assessment of critically ill or severely injured patients and those who need ongoing monitoring to evaluate response to anticoagulant therapy, she added.
Existing point-of-care coagulation assays have several shortcomings, Dr. Stavrou, of Case Western Reserve University, Cleveland, said during a press briefing at the conference. They are relatively insensitive, fail to measure platelet activity, or are only approved for specific subgroups of patients, such as those on warfarin, she specified.
To develop an alternative, Dr. Stavrou and her associates added a parallel-plate capacitive sensing structure to an inexpensive, disposable microfluidic biochip designed to test 9 microliters (less than one drop) of blood. They built the microsensor from biocompatible and chemically inert materials to minimize the chances of artificial contact activation.
To test the device, the researchers used calcium dichloride to induce coagulation in whole blood samples from 11 controls with normal aPTT and PT values. Time curves of output from the microsensor showed that coagulation consistently peaked within 4.5 to 6 minutes.
Next, the investigators tested blood from 12 patients with coagulopathies, including hemophilia A, hemophilia B, acquired von Willebrand factor defect, and congenital hypodysfibrinogenemia. These samples all yielded abnormal curves, with prolonged times to peak that ranged between 7 and 15 minutes – significantly exceeding those of healthy controls (P = .0002).
By plotting rates of true positives against rates of true negatives, the researchers obtained areas under the receiver operating curves of 100% for ClotChip, 78% for aPTT, and 57% for PT. In other words, ClotChip correctly identified all cases and controls in this small patient cohort, which neither aPTT or PT did.
Finally, the researchers used the microsensor to measure coagulation activity in normal blood samples that they treated with prostaglandin E2 to inhibit platelet aggregation. Normalized permittivity (an electrical measure) was significantly lower than in untreated control samples (P = .03), but time to peak values were the same in both groups. This finding confirms that the chip can identify abnormal platelet function, Dr. Stavrou said. “ClotChip is sensitive to the complete hemostasis process, exhibits better sensitivity and specificity than conventional coagulation assays, and discriminates between coagulation and platelet defects,” she concluded.
The investigators are recruiting volunteers for an expanded round of testing for the device, and are working to optimize construction to further enhance its sensitivity.
Dr. Stavrou and her coinvestigators had no relevant financial disclosures.
AT ASH 2016
Key clinical point: A prototype point-of-care microsensor perfectly distinguished patients with various coagulopathies from healthy controls.
Major finding: The area under the receiver operating characteristic curve was 100%, compared with 78% for aPTT and 59% for PT.
Data source: Oral and poster sessions at ASH 2016.
Disclosures: None of the investigators had relevant financial disclosures.
VIDEO: Combination venetoclax-LDAC therapy boosts overall survival in AML
SAN DIEGO – Combination therapy with the BCL-2 inhibitor venetoclax and low-dose cytarabine (LDAC) achieved a 61% overall response rate in older patients with treatment-naive acute myeloid leukemia, Andrew Wei, MBBS, PhD, reported at the annual meeting of the American Society of Hematology.
That is about three times higher than historically reported response rates for this deadly blood cancer, said Dr. Wei of Alfred Hospital in Melbourne, Australia. He discussed the findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The multicenter phase II study evaluated 28-cycles of venetoclax (600 mg, given orally) and LDAC (20 mg/m2 subcutaneously) in 53 treatment-naive AML patients aged 65 years and older, who were ineligible for intensive chemotherapy but had adequate liver and kidney function and an ECOG performance status between 0 and 2.
A total of 21% of patients had a complete remission, 33% had complete remission with incomplete marrow recovery, and 70% reached one of these endpoints during cycles 1 and 2. Common adverse events included vomiting, diarrhea, hypokalemia, and febrile neutropenia. Grade 3-4 adverse events included febrile neutropenia, hypokalemia, hypophosphatemia, and hypertension.
Researchers are planning larger randomized trials of venetoclax/LDAC combination therapy in AML, Dr. Wei said. Larger sample sizes will yield more data on how to best target this regimen based on prognostic indicators, such as gene mutations, he added.
Abbvie is the maker of venetoclax and sponsored the study. Dr. Wei disclosed a consulting relationship with Abbvie and ties to Novartis, Celgene, and several other pharmaceutical companies.
SAN DIEGO – Combination therapy with the BCL-2 inhibitor venetoclax and low-dose cytarabine (LDAC) achieved a 61% overall response rate in older patients with treatment-naive acute myeloid leukemia, Andrew Wei, MBBS, PhD, reported at the annual meeting of the American Society of Hematology.
That is about three times higher than historically reported response rates for this deadly blood cancer, said Dr. Wei of Alfred Hospital in Melbourne, Australia. He discussed the findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The multicenter phase II study evaluated 28-cycles of venetoclax (600 mg, given orally) and LDAC (20 mg/m2 subcutaneously) in 53 treatment-naive AML patients aged 65 years and older, who were ineligible for intensive chemotherapy but had adequate liver and kidney function and an ECOG performance status between 0 and 2.
A total of 21% of patients had a complete remission, 33% had complete remission with incomplete marrow recovery, and 70% reached one of these endpoints during cycles 1 and 2. Common adverse events included vomiting, diarrhea, hypokalemia, and febrile neutropenia. Grade 3-4 adverse events included febrile neutropenia, hypokalemia, hypophosphatemia, and hypertension.
Researchers are planning larger randomized trials of venetoclax/LDAC combination therapy in AML, Dr. Wei said. Larger sample sizes will yield more data on how to best target this regimen based on prognostic indicators, such as gene mutations, he added.
Abbvie is the maker of venetoclax and sponsored the study. Dr. Wei disclosed a consulting relationship with Abbvie and ties to Novartis, Celgene, and several other pharmaceutical companies.
SAN DIEGO – Combination therapy with the BCL-2 inhibitor venetoclax and low-dose cytarabine (LDAC) achieved a 61% overall response rate in older patients with treatment-naive acute myeloid leukemia, Andrew Wei, MBBS, PhD, reported at the annual meeting of the American Society of Hematology.
That is about three times higher than historically reported response rates for this deadly blood cancer, said Dr. Wei of Alfred Hospital in Melbourne, Australia. He discussed the findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
The multicenter phase II study evaluated 28-cycles of venetoclax (600 mg, given orally) and LDAC (20 mg/m2 subcutaneously) in 53 treatment-naive AML patients aged 65 years and older, who were ineligible for intensive chemotherapy but had adequate liver and kidney function and an ECOG performance status between 0 and 2.
A total of 21% of patients had a complete remission, 33% had complete remission with incomplete marrow recovery, and 70% reached one of these endpoints during cycles 1 and 2. Common adverse events included vomiting, diarrhea, hypokalemia, and febrile neutropenia. Grade 3-4 adverse events included febrile neutropenia, hypokalemia, hypophosphatemia, and hypertension.
Researchers are planning larger randomized trials of venetoclax/LDAC combination therapy in AML, Dr. Wei said. Larger sample sizes will yield more data on how to best target this regimen based on prognostic indicators, such as gene mutations, he added.
Abbvie is the maker of venetoclax and sponsored the study. Dr. Wei disclosed a consulting relationship with Abbvie and ties to Novartis, Celgene, and several other pharmaceutical companies.
AT ASH 2016
Key clinical point: Combination therapy with venetoclax and low-dose cytarabine (LDAC) achieved a high overall response rate in patients with AML.
Major finding: In all, 61% of patients achieved an overall response. Grade 3-4 adverse events included febrile neutropenia, hypokalemia, hypophosphatemia, and hypertension.
Data source: A multicenter phase II study of venetoclax (600 mg) and LDAC (20 mg/m2) in 53 treatment-naive AML patients aged 65 years and older, who were ineligible for intensive chemotherapy but had adequate liver and kidney function and an ECOG performance status of 0-2.
Disclosures: Abbvie is the maker of venetoclax and sponsored the study. Dr. Wei disclosed a consulting relationship with Abbvie and ties to Novartis, Celgene, and several other pharmaceutical companies.
ASH: Hemophilia B gene therapy posts strong update
SAN DIEGO – Patients with hemophilia B who received a single 1-hour infusion of the gene transfer therapy SPK-9001 achieved steady-state factor IX activity levels averaging 28% and persisting over 1,650 cumulative days of observation, according to updated results from a phase I/II trial.
All nine patients treated to date have exceeded the 12% steady-state factor IX activity level typically needed to prevent breakthrough bleeds, Katherine A. High, MD, said during a press briefing at the annual meeting of the American Society of Hematology. One patient infused himself once with factor IX after developing a suspected ankle bleed 2 days after treatment, Dr. High and her associates reported in the accompanying abstract.
This therapy works at a lower dose than previous factor IX gene transfer products and therefore has not caused the hepatotoxicity that halted their development, according to Dr. High, president and chief scientific officer of Spark Therapeutics, which makes SPK-9001. Two of nine patients developed an immune response to the viral capsid in the product, with a corresponding drop in factor IX activity levels, but the immune response was halted by tapering doses of corticosteroids, and patients maintained sufficient levels of factor IX activity to prevent breakthrough bleeds or the need for replacement factor, she said.
Because the virus capsid breaks down over time, a transient immune response to it “is not really a safety issue, but is an efficacy issue,” Dr. High emphasized. “If it is not caught in time, and patients are not given steroids promptly, they can lose the donated gene. Therefore, quick recognition is key.” Patients who develop an immune response to the viral capsid show sharp declines in factor IX activity levels, rises in baseline AST and ALT, and mononuclear cell reactivity, she explained during an interview.
The current standard of care for hemophilia B involves the cost and treatment burden of intravenous factor IX injections given one to three times weekly. Previous work evaluated factor IX gene transfer mediated by adeno-associated virus, but long-term factor IX activity levels did not reach the trough levels typically achieved with long-acting factor IX prophylaxis. Simply escalating the vector dose did not work because the viral capsid triggered immune-mediated hepatotoxicity, Dr. High noted.
To develop a more efficient product that works at lower doses, she and her associates created a recombinant vector containing a bioengineered adeno-associated virus capsid and a DNA sequence with a promoter designed to drive hepatic expression of a highly active variant of factor IX. To test the product, researchers in Mississippi, Pennsylvania, and California enrolled men aged 18-52 years with a confirmed diagnosis of hemophilia B (no more than 2 IU/dL or 2% endogenous factor IX) who had received at least 50 days of exposure to factor IX products and averaged at least four bleeding events per year requiring factor IX treatment or prophylaxis. Patients had no measurable inhibitory antibodies but otherwise represented the “general hemophilia B population,” Dr. High said. Five of nine patients had multiple target joints, liver disease associated with hepatitis C virus infection, or both. Each patient received a 1-hour infusion of 5 x 1011 vector genomes per body weight and was followed for 7-52 weeks.
Among seven patients who, by Nov. 30, 2016, had surpassed the 12 weeks needed to reach steady state factor IX expression levels, median steady-state level was 30% (range, 13%-38%), Dr. High reported. “Now we can give one quarter the dose [of adeno-associated virus vector] that was given before, and its driving factor IX expression levels five to eight times higher,” she concluded. Results for the first seven treated patients prompted Food and Drug Administration to give the product orphan drug designation in July 2016. Plans for phase III trials are underway, and researchers also are planning to investigate this approach to gene therapy in hemophilia A, Dr. High said.
Spark Therapeutics Inc. and Pfizer sponsored the study. Dr. High is president and chief scientific officer of Spark. Dr. George had no relevant financial disclosures.
SAN DIEGO – Patients with hemophilia B who received a single 1-hour infusion of the gene transfer therapy SPK-9001 achieved steady-state factor IX activity levels averaging 28% and persisting over 1,650 cumulative days of observation, according to updated results from a phase I/II trial.
All nine patients treated to date have exceeded the 12% steady-state factor IX activity level typically needed to prevent breakthrough bleeds, Katherine A. High, MD, said during a press briefing at the annual meeting of the American Society of Hematology. One patient infused himself once with factor IX after developing a suspected ankle bleed 2 days after treatment, Dr. High and her associates reported in the accompanying abstract.
This therapy works at a lower dose than previous factor IX gene transfer products and therefore has not caused the hepatotoxicity that halted their development, according to Dr. High, president and chief scientific officer of Spark Therapeutics, which makes SPK-9001. Two of nine patients developed an immune response to the viral capsid in the product, with a corresponding drop in factor IX activity levels, but the immune response was halted by tapering doses of corticosteroids, and patients maintained sufficient levels of factor IX activity to prevent breakthrough bleeds or the need for replacement factor, she said.
Because the virus capsid breaks down over time, a transient immune response to it “is not really a safety issue, but is an efficacy issue,” Dr. High emphasized. “If it is not caught in time, and patients are not given steroids promptly, they can lose the donated gene. Therefore, quick recognition is key.” Patients who develop an immune response to the viral capsid show sharp declines in factor IX activity levels, rises in baseline AST and ALT, and mononuclear cell reactivity, she explained during an interview.
The current standard of care for hemophilia B involves the cost and treatment burden of intravenous factor IX injections given one to three times weekly. Previous work evaluated factor IX gene transfer mediated by adeno-associated virus, but long-term factor IX activity levels did not reach the trough levels typically achieved with long-acting factor IX prophylaxis. Simply escalating the vector dose did not work because the viral capsid triggered immune-mediated hepatotoxicity, Dr. High noted.
To develop a more efficient product that works at lower doses, she and her associates created a recombinant vector containing a bioengineered adeno-associated virus capsid and a DNA sequence with a promoter designed to drive hepatic expression of a highly active variant of factor IX. To test the product, researchers in Mississippi, Pennsylvania, and California enrolled men aged 18-52 years with a confirmed diagnosis of hemophilia B (no more than 2 IU/dL or 2% endogenous factor IX) who had received at least 50 days of exposure to factor IX products and averaged at least four bleeding events per year requiring factor IX treatment or prophylaxis. Patients had no measurable inhibitory antibodies but otherwise represented the “general hemophilia B population,” Dr. High said. Five of nine patients had multiple target joints, liver disease associated with hepatitis C virus infection, or both. Each patient received a 1-hour infusion of 5 x 1011 vector genomes per body weight and was followed for 7-52 weeks.
Among seven patients who, by Nov. 30, 2016, had surpassed the 12 weeks needed to reach steady state factor IX expression levels, median steady-state level was 30% (range, 13%-38%), Dr. High reported. “Now we can give one quarter the dose [of adeno-associated virus vector] that was given before, and its driving factor IX expression levels five to eight times higher,” she concluded. Results for the first seven treated patients prompted Food and Drug Administration to give the product orphan drug designation in July 2016. Plans for phase III trials are underway, and researchers also are planning to investigate this approach to gene therapy in hemophilia A, Dr. High said.
Spark Therapeutics Inc. and Pfizer sponsored the study. Dr. High is president and chief scientific officer of Spark. Dr. George had no relevant financial disclosures.
SAN DIEGO – Patients with hemophilia B who received a single 1-hour infusion of the gene transfer therapy SPK-9001 achieved steady-state factor IX activity levels averaging 28% and persisting over 1,650 cumulative days of observation, according to updated results from a phase I/II trial.
All nine patients treated to date have exceeded the 12% steady-state factor IX activity level typically needed to prevent breakthrough bleeds, Katherine A. High, MD, said during a press briefing at the annual meeting of the American Society of Hematology. One patient infused himself once with factor IX after developing a suspected ankle bleed 2 days after treatment, Dr. High and her associates reported in the accompanying abstract.
This therapy works at a lower dose than previous factor IX gene transfer products and therefore has not caused the hepatotoxicity that halted their development, according to Dr. High, president and chief scientific officer of Spark Therapeutics, which makes SPK-9001. Two of nine patients developed an immune response to the viral capsid in the product, with a corresponding drop in factor IX activity levels, but the immune response was halted by tapering doses of corticosteroids, and patients maintained sufficient levels of factor IX activity to prevent breakthrough bleeds or the need for replacement factor, she said.
Because the virus capsid breaks down over time, a transient immune response to it “is not really a safety issue, but is an efficacy issue,” Dr. High emphasized. “If it is not caught in time, and patients are not given steroids promptly, they can lose the donated gene. Therefore, quick recognition is key.” Patients who develop an immune response to the viral capsid show sharp declines in factor IX activity levels, rises in baseline AST and ALT, and mononuclear cell reactivity, she explained during an interview.
The current standard of care for hemophilia B involves the cost and treatment burden of intravenous factor IX injections given one to three times weekly. Previous work evaluated factor IX gene transfer mediated by adeno-associated virus, but long-term factor IX activity levels did not reach the trough levels typically achieved with long-acting factor IX prophylaxis. Simply escalating the vector dose did not work because the viral capsid triggered immune-mediated hepatotoxicity, Dr. High noted.
To develop a more efficient product that works at lower doses, she and her associates created a recombinant vector containing a bioengineered adeno-associated virus capsid and a DNA sequence with a promoter designed to drive hepatic expression of a highly active variant of factor IX. To test the product, researchers in Mississippi, Pennsylvania, and California enrolled men aged 18-52 years with a confirmed diagnosis of hemophilia B (no more than 2 IU/dL or 2% endogenous factor IX) who had received at least 50 days of exposure to factor IX products and averaged at least four bleeding events per year requiring factor IX treatment or prophylaxis. Patients had no measurable inhibitory antibodies but otherwise represented the “general hemophilia B population,” Dr. High said. Five of nine patients had multiple target joints, liver disease associated with hepatitis C virus infection, or both. Each patient received a 1-hour infusion of 5 x 1011 vector genomes per body weight and was followed for 7-52 weeks.
Among seven patients who, by Nov. 30, 2016, had surpassed the 12 weeks needed to reach steady state factor IX expression levels, median steady-state level was 30% (range, 13%-38%), Dr. High reported. “Now we can give one quarter the dose [of adeno-associated virus vector] that was given before, and its driving factor IX expression levels five to eight times higher,” she concluded. Results for the first seven treated patients prompted Food and Drug Administration to give the product orphan drug designation in July 2016. Plans for phase III trials are underway, and researchers also are planning to investigate this approach to gene therapy in hemophilia A, Dr. High said.
Spark Therapeutics Inc. and Pfizer sponsored the study. Dr. High is president and chief scientific officer of Spark. Dr. George had no relevant financial disclosures.
AT ASH 2016
Key clinical point: Gene therapy with SPK-9001 continues to post strong results in patients with moderate to severe hemophilia B.
Major finding: As of Nov. 30, median steady-state factor IX levels were 30% (range, 13% to 38%). Two of nine patients developed an immune response to the adeno-associated virus capsid that appears to have been halted with tapering doses of corticosteroids.
Data source: An ongoing phase I/II trial of SPK-9001, dosed at 5 x 1011 vector genomes (vg)/kg body weight.
Disclosures: Spark Therapeutics Inc. and Pfizer sponsored the work. Dr. High is president and chief scientific officer of Spark. Dr. George had no relevant financial disclosures.
VIDEO: Hemophilia B gene therapy maintains factor IX levels averaging 28%
SAN DIEGO – Patients with hemophilia B who received a single infusion of the gene transfer therapy SPK-9001 achieved steady-state factor IX activity levels averaging 28% and persisting over 1,650 cumulative days of observation, according to updated results from a phase I/II trial.
All nine patients treated to date have exceeded the steady-state factor IX activity level typically needed to prevent breakthrough bleeds, Katherine A. High, MD, reported at the American Society of Hematology. There have been no confirmed bleeds, all patients remain off prophylactic factor IX, none have developed factor IX inhibitory antibodies, and Enzyme-Linked ImmunoSpot testing has uncovered no evidence of emergent reactivity to the gene product. Two patients developed an immune response to the viral capsid in the product, with a corresponding drop in factor IX activity levels. Tapering doses of corticosteroids halted the immune response and patients maintained sufficient levels of factor IX activity to prevent breakthrough bleeds or the need for replacement factor.
Spark Therapeutics Inc. and Pfizer sponsored the work. Dr. High is president and chief scientific officer of Spark. She discussed the trial in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN DIEGO – Patients with hemophilia B who received a single infusion of the gene transfer therapy SPK-9001 achieved steady-state factor IX activity levels averaging 28% and persisting over 1,650 cumulative days of observation, according to updated results from a phase I/II trial.
All nine patients treated to date have exceeded the steady-state factor IX activity level typically needed to prevent breakthrough bleeds, Katherine A. High, MD, reported at the American Society of Hematology. There have been no confirmed bleeds, all patients remain off prophylactic factor IX, none have developed factor IX inhibitory antibodies, and Enzyme-Linked ImmunoSpot testing has uncovered no evidence of emergent reactivity to the gene product. Two patients developed an immune response to the viral capsid in the product, with a corresponding drop in factor IX activity levels. Tapering doses of corticosteroids halted the immune response and patients maintained sufficient levels of factor IX activity to prevent breakthrough bleeds or the need for replacement factor.
Spark Therapeutics Inc. and Pfizer sponsored the work. Dr. High is president and chief scientific officer of Spark. She discussed the trial in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN DIEGO – Patients with hemophilia B who received a single infusion of the gene transfer therapy SPK-9001 achieved steady-state factor IX activity levels averaging 28% and persisting over 1,650 cumulative days of observation, according to updated results from a phase I/II trial.
All nine patients treated to date have exceeded the steady-state factor IX activity level typically needed to prevent breakthrough bleeds, Katherine A. High, MD, reported at the American Society of Hematology. There have been no confirmed bleeds, all patients remain off prophylactic factor IX, none have developed factor IX inhibitory antibodies, and Enzyme-Linked ImmunoSpot testing has uncovered no evidence of emergent reactivity to the gene product. Two patients developed an immune response to the viral capsid in the product, with a corresponding drop in factor IX activity levels. Tapering doses of corticosteroids halted the immune response and patients maintained sufficient levels of factor IX activity to prevent breakthrough bleeds or the need for replacement factor.
Spark Therapeutics Inc. and Pfizer sponsored the work. Dr. High is president and chief scientific officer of Spark. She discussed the trial in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASH 2016
ASH: Novel microcapsules show promise in hemophilia A with inhibitory antibodies
SAN DIEGO – Novel microcapsules loaded with factor VIII outperformed systemic factor VIII infusions in a model of hemophilia A with inhibitory antibodies, Caroline E. Hansen reported at the annual meeting of the American Society of Hematology.
“This is a completely new paradigm that uses platelet biomechanics to target and deliver a drug,” Ms. Hansen said at a press briefing.
To create the microcapsules, the investigators deposited alternatingly charged layers of polyelectrolytes, poly-L-lysine, and poly-L-glutamic acid onto a calcium carbonate core covered with factor VIII and dextran. They added fibrinogen to the final polyelectrolyte layer and then chelated out the innermost core, leaving the dextran layer as a shield between factor VIII and the outside of the microcapsule. Initial in vitro experiments showed that the microcapsules adhered to platelets and were incorporated into fibrin networks when platelets were activated, Ms. Hansen reported. Because the microcapsules only ruptured upon platelet contraction, factor VIII was only delivered to actively forming clots as intended, she added.
As a next step, the researchers perfused recalcified whole blood and platelet-poor plasma into a collagen and tissue factor patch designed to mimic vascular injury, and then measured fibrin fluorescence on the patch. Microcapsules lacking dextran, fibrinogen, or loaded factor VIII did not work – a treated sample and a phosphate-buffered saline (PBS) control yielded statistically similar fibrin production. However, complete microcapsules loaded with 0.01 U/mL factor VIII produced four times more fibrin than systemic infusion of 0.05 U/mL factor VIII.
“These were really promising results but we want to take a step back and see if a clot would form in the presence of inhibitory antibodies,” Ms. Hansen said. Accordingly, they added factor VIII inhibitory antibody 2-76 into blood samples from healthy donors. The microcapsules triggered 2.7 times more fibrin production in this setting than systemic treatment did (P less than .05). “This increased efficacy is likely due to the microcapsule shielding effect on factor VIII, preventing exposure to inhibitory antibodies,” Ms. Hansen and her associates concluded in their abstract.
The investigators are now studying the extent to which the microcapsules induce thrombin production, and how agents such as blebbistatin, ROCK, and myosin affect platelet contraction force and the efficiency of the microcapsule.
Ms. Hansen had no disclosures.
SAN DIEGO – Novel microcapsules loaded with factor VIII outperformed systemic factor VIII infusions in a model of hemophilia A with inhibitory antibodies, Caroline E. Hansen reported at the annual meeting of the American Society of Hematology.
“This is a completely new paradigm that uses platelet biomechanics to target and deliver a drug,” Ms. Hansen said at a press briefing.
To create the microcapsules, the investigators deposited alternatingly charged layers of polyelectrolytes, poly-L-lysine, and poly-L-glutamic acid onto a calcium carbonate core covered with factor VIII and dextran. They added fibrinogen to the final polyelectrolyte layer and then chelated out the innermost core, leaving the dextran layer as a shield between factor VIII and the outside of the microcapsule. Initial in vitro experiments showed that the microcapsules adhered to platelets and were incorporated into fibrin networks when platelets were activated, Ms. Hansen reported. Because the microcapsules only ruptured upon platelet contraction, factor VIII was only delivered to actively forming clots as intended, she added.
As a next step, the researchers perfused recalcified whole blood and platelet-poor plasma into a collagen and tissue factor patch designed to mimic vascular injury, and then measured fibrin fluorescence on the patch. Microcapsules lacking dextran, fibrinogen, or loaded factor VIII did not work – a treated sample and a phosphate-buffered saline (PBS) control yielded statistically similar fibrin production. However, complete microcapsules loaded with 0.01 U/mL factor VIII produced four times more fibrin than systemic infusion of 0.05 U/mL factor VIII.
“These were really promising results but we want to take a step back and see if a clot would form in the presence of inhibitory antibodies,” Ms. Hansen said. Accordingly, they added factor VIII inhibitory antibody 2-76 into blood samples from healthy donors. The microcapsules triggered 2.7 times more fibrin production in this setting than systemic treatment did (P less than .05). “This increased efficacy is likely due to the microcapsule shielding effect on factor VIII, preventing exposure to inhibitory antibodies,” Ms. Hansen and her associates concluded in their abstract.
The investigators are now studying the extent to which the microcapsules induce thrombin production, and how agents such as blebbistatin, ROCK, and myosin affect platelet contraction force and the efficiency of the microcapsule.
Ms. Hansen had no disclosures.
SAN DIEGO – Novel microcapsules loaded with factor VIII outperformed systemic factor VIII infusions in a model of hemophilia A with inhibitory antibodies, Caroline E. Hansen reported at the annual meeting of the American Society of Hematology.
“This is a completely new paradigm that uses platelet biomechanics to target and deliver a drug,” Ms. Hansen said at a press briefing.
To create the microcapsules, the investigators deposited alternatingly charged layers of polyelectrolytes, poly-L-lysine, and poly-L-glutamic acid onto a calcium carbonate core covered with factor VIII and dextran. They added fibrinogen to the final polyelectrolyte layer and then chelated out the innermost core, leaving the dextran layer as a shield between factor VIII and the outside of the microcapsule. Initial in vitro experiments showed that the microcapsules adhered to platelets and were incorporated into fibrin networks when platelets were activated, Ms. Hansen reported. Because the microcapsules only ruptured upon platelet contraction, factor VIII was only delivered to actively forming clots as intended, she added.
As a next step, the researchers perfused recalcified whole blood and platelet-poor plasma into a collagen and tissue factor patch designed to mimic vascular injury, and then measured fibrin fluorescence on the patch. Microcapsules lacking dextran, fibrinogen, or loaded factor VIII did not work – a treated sample and a phosphate-buffered saline (PBS) control yielded statistically similar fibrin production. However, complete microcapsules loaded with 0.01 U/mL factor VIII produced four times more fibrin than systemic infusion of 0.05 U/mL factor VIII.
“These were really promising results but we want to take a step back and see if a clot would form in the presence of inhibitory antibodies,” Ms. Hansen said. Accordingly, they added factor VIII inhibitory antibody 2-76 into blood samples from healthy donors. The microcapsules triggered 2.7 times more fibrin production in this setting than systemic treatment did (P less than .05). “This increased efficacy is likely due to the microcapsule shielding effect on factor VIII, preventing exposure to inhibitory antibodies,” Ms. Hansen and her associates concluded in their abstract.
The investigators are now studying the extent to which the microcapsules induce thrombin production, and how agents such as blebbistatin, ROCK, and myosin affect platelet contraction force and the efficiency of the microcapsule.
Ms. Hansen had no disclosures.
AT ASH 2016
Key clinical point: Novel microcapsules loaded with factor VIII outperformed systemic factor VIII infusions in an in vitro model of hemophilia A with inhibitory antibodies.
Major finding: In an in vitro model of this disease state, the microcapsules triggered 2.7 times more fibrin production than systemic treatment with factor VIII (P less than .05).
Data source: A multicenter laboratory study.
Disclosures: Ms. Hansen had no relevant financial disclosures.
VIDEO: Novel microcapsules show promise in hemophilia A with inhibitory antibodies
SAN DIEGO – Novel microcapsules loaded with factor VIII outperformed systemic factor VIII infusions in models of hemophilia A with inhibitory antibodies, Caroline E. Hansen reported at the annual meeting of the American Society of Hematology.
“This is a completely new paradigm that uses platelet biomechanics to target and deliver a drug,” said Ms. Hansen of Georgia Institute of Technology, Atlanta.
The microcapsules are designed to mechanically shield factor VIII from the immune system. When they reached a modeled site of vascular injury, they contracted and released factor VIII. Initial work showed that this approach triggered significantly more fibrin production in a developing clot than did systemic infusions of factor VIII.
Ms. Hansen had no disclosures. She discussed the findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN DIEGO – Novel microcapsules loaded with factor VIII outperformed systemic factor VIII infusions in models of hemophilia A with inhibitory antibodies, Caroline E. Hansen reported at the annual meeting of the American Society of Hematology.
“This is a completely new paradigm that uses platelet biomechanics to target and deliver a drug,” said Ms. Hansen of Georgia Institute of Technology, Atlanta.
The microcapsules are designed to mechanically shield factor VIII from the immune system. When they reached a modeled site of vascular injury, they contracted and released factor VIII. Initial work showed that this approach triggered significantly more fibrin production in a developing clot than did systemic infusions of factor VIII.
Ms. Hansen had no disclosures. She discussed the findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
SAN DIEGO – Novel microcapsules loaded with factor VIII outperformed systemic factor VIII infusions in models of hemophilia A with inhibitory antibodies, Caroline E. Hansen reported at the annual meeting of the American Society of Hematology.
“This is a completely new paradigm that uses platelet biomechanics to target and deliver a drug,” said Ms. Hansen of Georgia Institute of Technology, Atlanta.
The microcapsules are designed to mechanically shield factor VIII from the immune system. When they reached a modeled site of vascular injury, they contracted and released factor VIII. Initial work showed that this approach triggered significantly more fibrin production in a developing clot than did systemic infusions of factor VIII.
Ms. Hansen had no disclosures. She discussed the findings in a video interview.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT ASH 2016
Key clinical point: Novel microcapsules loaded with factor VIII outperformed systemic factor VIII infusions in an in vitro model of hemophilia A with inhibitory antibodies.
Major finding: In an in vitro model, the microcapsules triggered 2.7 times more fibrin production than systemic treatment with factor VIII (P less than .05).
Data source: A multicenter laboratory study.
Disclosures: Ms. Hansen had no relevant financial disclosures.
VIDEO: Y90 radioembolization beat chemoembolization in liver cancer
Liver cancer took nearly four times longer to progress after yttrium-90 (Y90) radioembolization than after conventional transarterial chemoembolization (cTACE), according to a single-center, randomized, phase II trial of 45 patients reported in the December issue of Gastroenterology (2016 Aug 26. doi: 10.1053/j.gastro.2016.08.029).
Median time to progression remained unreached more than 26 months after patients underwent Y90 treatment, but was only 6.8 months in the cTACE group (P = .001), Riad Salem, MD, and his associates at Northwestern University,Chicago, reported. Slow accrual limited the study size, but a post-hoc analysis showed that Y90 would have a 97% chance of significantly outperforming chemoembolization if the study had reached its enrollment target, even if the difference in time to progression was less pronounced. Furthermore, Y90 significantly outperformed chemoembolization in a competing risk analysis that accounted for liver transplantation and death, the researchers said.
Conventional transarterial chemoembolization is used in intermediate-stage liver cancer when ablation is contraindicated. However, retrospective studies have favored Y90 radioembolization, a minimally invasive procedure in which a clinician implants radioactive micron-sized particles loaded with Y90 inside blood vessels supplying a tumor. To further study this approach, the investigators randomly assigned patients with unresectable, unablatable hepatocellular carcinoma without vascular invasion, who had Child-Pugh scores of A or B, serum bilirubin levels up to 2 mg/dL, and liver enzymes up to five times the normal upper limit, to undergo selective Y90 at a dose of 120 Gy, or lipiodol-based chemoembolization at a dose of 75 mg/m2.
Source: American Gastroenterological Association
Of 179 eligible patients, 134 (75%) declined to participate in research, opted for other trials, or chose one protocol over the other. Consequently, only 21 patients were assigned to cTACE, while 24 underwent Y90. The groups resembled each other clinically and demographically at baseline, although Y90 patients tended to have more portal hypertension and higher serum bilirubin levels. No patients died within 30 days after treatment. Each group had one case of common femoral artery pseudoaneurysm. The Y90 patients tended to have more fatigue (P = .08), and had higher rates of diarrhea (P = .03) and hypoalbuminemia (P less than .001).
Despite the small group sizes, patients were about 88% less likely to progress at a given time point after Y90, compared with cTACE (hazard ratio, 0.12; 95% confidence interval, 0.03-0.56; P = .007). To explore what might have happened had the study reached target enrollment, the researchers added another 79 hypothetical patients at the 5.1-fold higher hazard ratio (0.625) that they had used in the power calculation. The results showed that Y90 had a 97% chance of statistically outperforming cTACE under these conditions.
Inverse probability of censoring weighting, which is performed to control for dependent censoring between groups, also showed that time to progression was significantly longer with Y90 than with cTACE, the investigators said. “While the relatively low sample size is acknowledged, the seminal studies establishing cTACE as the standard of care were also limited in sample size, [were] single center, and enrolled mostly Child-Pugh A patients,” they emphasized. “Our time to progression results favoring Y90 are in line with other uncontrolled retrospective reports in patients with compromised liver function, [but] our study validates such findings with prospective randomized level I evidence.”
The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.
There are several practical reasons to favor Y90 radioembolization over chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC): Y90 is less embolic and thus can be used to treat the entire lobe, patients experience fewer immediate embolization side effects, and anecdotally, the duration of response seems to be somewhat longer. However, until now, the only data supporting Y90 have consisted of uncontrolled series, as compared with TACE, which is supported by a number of randomized trials and meta-analyses.
Should we believe the results? My feeling is yes, with only minor caveats. The first is that the study was stopped early because of poor enrollment, with fewer than half the planned sample size. However, interim analysis methods were applied and predicted a 97% probability that the answer would be the same if enrollment had continued. Secondly, it was surprising to see that the transplant rates were nearly double in the Y90 group (13 transplanted out of 24) versus the TACE group (7 transplanted out of 21). These numbers are small, so the difference may have been because of chance, but it suggests that the mechanism for superiority of Y90 may be at least partially via transplantation.
In summary, Y90 appears superior to TACE in the first (small) randomized comparison. Specific scenarios where Y90 may be particularly preferred include multiple small lesions, and lesions without much arterial enhancement. I hope these data will be used to perform cost-effectiveness analyses in order to justify the increased cost to third-party payers.
Michael L. Volk, MD, MSc, AGAF, is medical director of liver transplantation, division chief, gastroenterology and hepatology, Loma Linda (Calif.) University Health. He has no conflicts of interest.
There are several practical reasons to favor Y90 radioembolization over chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC): Y90 is less embolic and thus can be used to treat the entire lobe, patients experience fewer immediate embolization side effects, and anecdotally, the duration of response seems to be somewhat longer. However, until now, the only data supporting Y90 have consisted of uncontrolled series, as compared with TACE, which is supported by a number of randomized trials and meta-analyses.
Should we believe the results? My feeling is yes, with only minor caveats. The first is that the study was stopped early because of poor enrollment, with fewer than half the planned sample size. However, interim analysis methods were applied and predicted a 97% probability that the answer would be the same if enrollment had continued. Secondly, it was surprising to see that the transplant rates were nearly double in the Y90 group (13 transplanted out of 24) versus the TACE group (7 transplanted out of 21). These numbers are small, so the difference may have been because of chance, but it suggests that the mechanism for superiority of Y90 may be at least partially via transplantation.
In summary, Y90 appears superior to TACE in the first (small) randomized comparison. Specific scenarios where Y90 may be particularly preferred include multiple small lesions, and lesions without much arterial enhancement. I hope these data will be used to perform cost-effectiveness analyses in order to justify the increased cost to third-party payers.
Michael L. Volk, MD, MSc, AGAF, is medical director of liver transplantation, division chief, gastroenterology and hepatology, Loma Linda (Calif.) University Health. He has no conflicts of interest.
There are several practical reasons to favor Y90 radioembolization over chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC): Y90 is less embolic and thus can be used to treat the entire lobe, patients experience fewer immediate embolization side effects, and anecdotally, the duration of response seems to be somewhat longer. However, until now, the only data supporting Y90 have consisted of uncontrolled series, as compared with TACE, which is supported by a number of randomized trials and meta-analyses.
Should we believe the results? My feeling is yes, with only minor caveats. The first is that the study was stopped early because of poor enrollment, with fewer than half the planned sample size. However, interim analysis methods were applied and predicted a 97% probability that the answer would be the same if enrollment had continued. Secondly, it was surprising to see that the transplant rates were nearly double in the Y90 group (13 transplanted out of 24) versus the TACE group (7 transplanted out of 21). These numbers are small, so the difference may have been because of chance, but it suggests that the mechanism for superiority of Y90 may be at least partially via transplantation.
In summary, Y90 appears superior to TACE in the first (small) randomized comparison. Specific scenarios where Y90 may be particularly preferred include multiple small lesions, and lesions without much arterial enhancement. I hope these data will be used to perform cost-effectiveness analyses in order to justify the increased cost to third-party payers.
Michael L. Volk, MD, MSc, AGAF, is medical director of liver transplantation, division chief, gastroenterology and hepatology, Loma Linda (Calif.) University Health. He has no conflicts of interest.
Liver cancer took nearly four times longer to progress after yttrium-90 (Y90) radioembolization than after conventional transarterial chemoembolization (cTACE), according to a single-center, randomized, phase II trial of 45 patients reported in the December issue of Gastroenterology (2016 Aug 26. doi: 10.1053/j.gastro.2016.08.029).
Median time to progression remained unreached more than 26 months after patients underwent Y90 treatment, but was only 6.8 months in the cTACE group (P = .001), Riad Salem, MD, and his associates at Northwestern University,Chicago, reported. Slow accrual limited the study size, but a post-hoc analysis showed that Y90 would have a 97% chance of significantly outperforming chemoembolization if the study had reached its enrollment target, even if the difference in time to progression was less pronounced. Furthermore, Y90 significantly outperformed chemoembolization in a competing risk analysis that accounted for liver transplantation and death, the researchers said.
Conventional transarterial chemoembolization is used in intermediate-stage liver cancer when ablation is contraindicated. However, retrospective studies have favored Y90 radioembolization, a minimally invasive procedure in which a clinician implants radioactive micron-sized particles loaded with Y90 inside blood vessels supplying a tumor. To further study this approach, the investigators randomly assigned patients with unresectable, unablatable hepatocellular carcinoma without vascular invasion, who had Child-Pugh scores of A or B, serum bilirubin levels up to 2 mg/dL, and liver enzymes up to five times the normal upper limit, to undergo selective Y90 at a dose of 120 Gy, or lipiodol-based chemoembolization at a dose of 75 mg/m2.
Source: American Gastroenterological Association
Of 179 eligible patients, 134 (75%) declined to participate in research, opted for other trials, or chose one protocol over the other. Consequently, only 21 patients were assigned to cTACE, while 24 underwent Y90. The groups resembled each other clinically and demographically at baseline, although Y90 patients tended to have more portal hypertension and higher serum bilirubin levels. No patients died within 30 days after treatment. Each group had one case of common femoral artery pseudoaneurysm. The Y90 patients tended to have more fatigue (P = .08), and had higher rates of diarrhea (P = .03) and hypoalbuminemia (P less than .001).
Despite the small group sizes, patients were about 88% less likely to progress at a given time point after Y90, compared with cTACE (hazard ratio, 0.12; 95% confidence interval, 0.03-0.56; P = .007). To explore what might have happened had the study reached target enrollment, the researchers added another 79 hypothetical patients at the 5.1-fold higher hazard ratio (0.625) that they had used in the power calculation. The results showed that Y90 had a 97% chance of statistically outperforming cTACE under these conditions.
Inverse probability of censoring weighting, which is performed to control for dependent censoring between groups, also showed that time to progression was significantly longer with Y90 than with cTACE, the investigators said. “While the relatively low sample size is acknowledged, the seminal studies establishing cTACE as the standard of care were also limited in sample size, [were] single center, and enrolled mostly Child-Pugh A patients,” they emphasized. “Our time to progression results favoring Y90 are in line with other uncontrolled retrospective reports in patients with compromised liver function, [but] our study validates such findings with prospective randomized level I evidence.”
The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.
Liver cancer took nearly four times longer to progress after yttrium-90 (Y90) radioembolization than after conventional transarterial chemoembolization (cTACE), according to a single-center, randomized, phase II trial of 45 patients reported in the December issue of Gastroenterology (2016 Aug 26. doi: 10.1053/j.gastro.2016.08.029).
Median time to progression remained unreached more than 26 months after patients underwent Y90 treatment, but was only 6.8 months in the cTACE group (P = .001), Riad Salem, MD, and his associates at Northwestern University,Chicago, reported. Slow accrual limited the study size, but a post-hoc analysis showed that Y90 would have a 97% chance of significantly outperforming chemoembolization if the study had reached its enrollment target, even if the difference in time to progression was less pronounced. Furthermore, Y90 significantly outperformed chemoembolization in a competing risk analysis that accounted for liver transplantation and death, the researchers said.
Conventional transarterial chemoembolization is used in intermediate-stage liver cancer when ablation is contraindicated. However, retrospective studies have favored Y90 radioembolization, a minimally invasive procedure in which a clinician implants radioactive micron-sized particles loaded with Y90 inside blood vessels supplying a tumor. To further study this approach, the investigators randomly assigned patients with unresectable, unablatable hepatocellular carcinoma without vascular invasion, who had Child-Pugh scores of A or B, serum bilirubin levels up to 2 mg/dL, and liver enzymes up to five times the normal upper limit, to undergo selective Y90 at a dose of 120 Gy, or lipiodol-based chemoembolization at a dose of 75 mg/m2.
Source: American Gastroenterological Association
Of 179 eligible patients, 134 (75%) declined to participate in research, opted for other trials, or chose one protocol over the other. Consequently, only 21 patients were assigned to cTACE, while 24 underwent Y90. The groups resembled each other clinically and demographically at baseline, although Y90 patients tended to have more portal hypertension and higher serum bilirubin levels. No patients died within 30 days after treatment. Each group had one case of common femoral artery pseudoaneurysm. The Y90 patients tended to have more fatigue (P = .08), and had higher rates of diarrhea (P = .03) and hypoalbuminemia (P less than .001).
Despite the small group sizes, patients were about 88% less likely to progress at a given time point after Y90, compared with cTACE (hazard ratio, 0.12; 95% confidence interval, 0.03-0.56; P = .007). To explore what might have happened had the study reached target enrollment, the researchers added another 79 hypothetical patients at the 5.1-fold higher hazard ratio (0.625) that they had used in the power calculation. The results showed that Y90 had a 97% chance of statistically outperforming cTACE under these conditions.
Inverse probability of censoring weighting, which is performed to control for dependent censoring between groups, also showed that time to progression was significantly longer with Y90 than with cTACE, the investigators said. “While the relatively low sample size is acknowledged, the seminal studies establishing cTACE as the standard of care were also limited in sample size, [were] single center, and enrolled mostly Child-Pugh A patients,” they emphasized. “Our time to progression results favoring Y90 are in line with other uncontrolled retrospective reports in patients with compromised liver function, [but] our study validates such findings with prospective randomized level I evidence.”
The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.
FROM GASTROENTEROLOGY
Key clinical point: Yttrium-90 (Y90) radioembolization outperformed chemoembolization in hepatocellular carcinoma.
Major finding: Median time to progression was not reached at more than 26 months in the Y90 arm, vs. 6.8 months in the chemoembolization arm (P = .001).
Data source: A randomized phase II trial of 45 patients with hepatocellular carcinoma of Barcelona Clinic Liver Cancer stages A or B.
Disclosures: The National Institutes of Health and the SIR Foundation provided funding. Dr. Salem and two coinvestigators reported serving as advisors to BTG. The other coinvestigators reported having no conflicts of interest.
Mobile health indexes accurately detected active inflammatory bowel disease
Mobile health indexes for remotely monitoring Crohn’s disease and ulcerative colitis accurately identified clinically active disease and changed significantly as disease activity did, researchers reported in the December issue of Clinical Gastroenterology and Hepatology.
The mobile health index for Crohn’s disease predicted clinical disease activity with an area under the receiver operating characteristic curve (AUC) of 0.90, Welmoed K. van Deen, MD, of the University of California, Los Angeles, and her associates wrote in Clinical Gastroenterology and Hepatology. The AUC for the ulcerative colitis index for ulcerative colitis was very similar, at 0.91. “The [mobile health indexes] are specifically designed for implementation on a mobile application, and are currently available to patients with IBD [inflammatory bowel disease] treated at the UCLA Center for IBD,” the researchers said. “Prospective, randomized studies need to assess the effect of remote monitoring on disease control, quality of life, patient satisfaction, and health care costs.”
Inspired by the lack of smartphone applications for remotely managing inflammatory bowel disease, the researchers administered comprehensive disease-specific questionnaires to 110 patients with Crohn’s disease and 109 patients with ulcerative colitis who visited the UCLA IBD center in 2013 and 2014. They compared patient-reported outcomes across 10 domains of disease activity with scores on a number of existing disease activity indexes, and used logistic regression to identify which self-reported outcomes best predicted disease activity in both Crohn’s disease and ulcerative colitis (Clin Gastroenterol Hepatol. 2015 Nov 18. doi: 10.1016/j.cgh.2015.10.035).
The resulting Crohn’s disease mobile health index asked how many liquid or “very soft” stools patients had per day, if they had abdominal pain, and how they would rate their well-being and level of disease control on scales ranging between 0 and 10. The ulcerative colitis mobile health index asked about number of stools the day before and had patients score abdominal pain, frequency of rectal bleeding, and level of disease control between 0 and 10. The researchers also validated each mobile health index in multicenter cohorts of 301 patients with Crohn’s disease and 265 patients with ulcerative colitis.
Each mobile health index detected clinical disease activity with about 90% accuracy, compared with standard measures, including the Crohn’s disease activity index and the Harvey Bradshaw index for Crohn’s disease, the partial Mayo score, the simple clinical colitis activity index, and the modified Truelove and Witts index for ulcerative colitis. But the mobile indexes detected endoscopic disease activity less accurately, with AUCs of 0.82 for ulcerative colitis and only 0.63 for Crohn’s disease. “As previously shown, ulcerative colitis clinical disease activity highly correlates with endoscopic disease activity, whereas correlation between Crohn’s disease symptoms and endoscopic findings is poor,” the researchers noted. However, both mobile indexes reliably detected changes in disease activity, varying significantly depending on whether patients were clinically improved, stable, or worse, regardless of whether they had Crohn’s disease (P = .003) or ulcerative colitis (P = .0025).
To explore intrapatient reliability, the researchers also compared initial and follow-up mobile health index results for subgroups of 40 Crohn’s disease patients tested a median of 21 hours apart, and 37 ulcerative colitis patients tested a median of 23 hours apart. In both cases, the intraclass correlation coefficient reached 0.94 (95% confidence interval, 0.89-0.97). “Cloud-based health technologies are predicted to revolutionize care delivery and patient engagement,” the investigators commented. “Patients can participate in their care by signaling meaningful health outcomes during year-round monitoring. Barriers for more widespread implementation of mobile health in inflammatory bowel disease care include policies affecting reimbursement and regulatory requirements, and privacy and security concerns.”
Genova Diagnostics provided stool collection kits and fecal calprotectin testing. The investigators had no disclosures.
To make mobile applications for inflammatory bowel disease valuable, it is critical to accurately capture disease activity in a consistent and reproducible manner. With this in mind, Dr. Van Deen and colleagues designed and evaluated specific “mobile health indexes” (mHIs) for patients with Crohn’s disease and ulcerative colitis.
Patients were invited to complete validated questionnaires assessing patient-reported outcomes (PROs) and clinical disease activity. PROs across 10 domains with the strongest correlation to clinical disease activity scores were identified and used to generate the mobile health indexes.
Strengths of this particular study include the prospective design that incorporated reliability assessments and independent validation cohorts. Potential weaknesses include patient recall bias, small sample size, and lack of knowledge on how language and numerical scales were interpreted across health literacy levels and cultural backgrounds. Nevertheless, these mobile health indexes have promise, both as disease-monitoring and engagement tools, whose clinical impact has yet to be fully realized.
Lauren K. Tormey, MD, is an assistant professor of medicine at the Geisel School of Medicine at Dartmouth and member of the Dartmouth-Hitchcock Inflammatory Bowel Disease Center in Lebanon, N.H. She discloses no conflicts.
To make mobile applications for inflammatory bowel disease valuable, it is critical to accurately capture disease activity in a consistent and reproducible manner. With this in mind, Dr. Van Deen and colleagues designed and evaluated specific “mobile health indexes” (mHIs) for patients with Crohn’s disease and ulcerative colitis.
Patients were invited to complete validated questionnaires assessing patient-reported outcomes (PROs) and clinical disease activity. PROs across 10 domains with the strongest correlation to clinical disease activity scores were identified and used to generate the mobile health indexes.
Strengths of this particular study include the prospective design that incorporated reliability assessments and independent validation cohorts. Potential weaknesses include patient recall bias, small sample size, and lack of knowledge on how language and numerical scales were interpreted across health literacy levels and cultural backgrounds. Nevertheless, these mobile health indexes have promise, both as disease-monitoring and engagement tools, whose clinical impact has yet to be fully realized.
Lauren K. Tormey, MD, is an assistant professor of medicine at the Geisel School of Medicine at Dartmouth and member of the Dartmouth-Hitchcock Inflammatory Bowel Disease Center in Lebanon, N.H. She discloses no conflicts.
To make mobile applications for inflammatory bowel disease valuable, it is critical to accurately capture disease activity in a consistent and reproducible manner. With this in mind, Dr. Van Deen and colleagues designed and evaluated specific “mobile health indexes” (mHIs) for patients with Crohn’s disease and ulcerative colitis.
Patients were invited to complete validated questionnaires assessing patient-reported outcomes (PROs) and clinical disease activity. PROs across 10 domains with the strongest correlation to clinical disease activity scores were identified and used to generate the mobile health indexes.
Strengths of this particular study include the prospective design that incorporated reliability assessments and independent validation cohorts. Potential weaknesses include patient recall bias, small sample size, and lack of knowledge on how language and numerical scales were interpreted across health literacy levels and cultural backgrounds. Nevertheless, these mobile health indexes have promise, both as disease-monitoring and engagement tools, whose clinical impact has yet to be fully realized.
Lauren K. Tormey, MD, is an assistant professor of medicine at the Geisel School of Medicine at Dartmouth and member of the Dartmouth-Hitchcock Inflammatory Bowel Disease Center in Lebanon, N.H. She discloses no conflicts.
Mobile health indexes for remotely monitoring Crohn’s disease and ulcerative colitis accurately identified clinically active disease and changed significantly as disease activity did, researchers reported in the December issue of Clinical Gastroenterology and Hepatology.
The mobile health index for Crohn’s disease predicted clinical disease activity with an area under the receiver operating characteristic curve (AUC) of 0.90, Welmoed K. van Deen, MD, of the University of California, Los Angeles, and her associates wrote in Clinical Gastroenterology and Hepatology. The AUC for the ulcerative colitis index for ulcerative colitis was very similar, at 0.91. “The [mobile health indexes] are specifically designed for implementation on a mobile application, and are currently available to patients with IBD [inflammatory bowel disease] treated at the UCLA Center for IBD,” the researchers said. “Prospective, randomized studies need to assess the effect of remote monitoring on disease control, quality of life, patient satisfaction, and health care costs.”
Inspired by the lack of smartphone applications for remotely managing inflammatory bowel disease, the researchers administered comprehensive disease-specific questionnaires to 110 patients with Crohn’s disease and 109 patients with ulcerative colitis who visited the UCLA IBD center in 2013 and 2014. They compared patient-reported outcomes across 10 domains of disease activity with scores on a number of existing disease activity indexes, and used logistic regression to identify which self-reported outcomes best predicted disease activity in both Crohn’s disease and ulcerative colitis (Clin Gastroenterol Hepatol. 2015 Nov 18. doi: 10.1016/j.cgh.2015.10.035).
The resulting Crohn’s disease mobile health index asked how many liquid or “very soft” stools patients had per day, if they had abdominal pain, and how they would rate their well-being and level of disease control on scales ranging between 0 and 10. The ulcerative colitis mobile health index asked about number of stools the day before and had patients score abdominal pain, frequency of rectal bleeding, and level of disease control between 0 and 10. The researchers also validated each mobile health index in multicenter cohorts of 301 patients with Crohn’s disease and 265 patients with ulcerative colitis.
Each mobile health index detected clinical disease activity with about 90% accuracy, compared with standard measures, including the Crohn’s disease activity index and the Harvey Bradshaw index for Crohn’s disease, the partial Mayo score, the simple clinical colitis activity index, and the modified Truelove and Witts index for ulcerative colitis. But the mobile indexes detected endoscopic disease activity less accurately, with AUCs of 0.82 for ulcerative colitis and only 0.63 for Crohn’s disease. “As previously shown, ulcerative colitis clinical disease activity highly correlates with endoscopic disease activity, whereas correlation between Crohn’s disease symptoms and endoscopic findings is poor,” the researchers noted. However, both mobile indexes reliably detected changes in disease activity, varying significantly depending on whether patients were clinically improved, stable, or worse, regardless of whether they had Crohn’s disease (P = .003) or ulcerative colitis (P = .0025).
To explore intrapatient reliability, the researchers also compared initial and follow-up mobile health index results for subgroups of 40 Crohn’s disease patients tested a median of 21 hours apart, and 37 ulcerative colitis patients tested a median of 23 hours apart. In both cases, the intraclass correlation coefficient reached 0.94 (95% confidence interval, 0.89-0.97). “Cloud-based health technologies are predicted to revolutionize care delivery and patient engagement,” the investigators commented. “Patients can participate in their care by signaling meaningful health outcomes during year-round monitoring. Barriers for more widespread implementation of mobile health in inflammatory bowel disease care include policies affecting reimbursement and regulatory requirements, and privacy and security concerns.”
Genova Diagnostics provided stool collection kits and fecal calprotectin testing. The investigators had no disclosures.
Mobile health indexes for remotely monitoring Crohn’s disease and ulcerative colitis accurately identified clinically active disease and changed significantly as disease activity did, researchers reported in the December issue of Clinical Gastroenterology and Hepatology.
The mobile health index for Crohn’s disease predicted clinical disease activity with an area under the receiver operating characteristic curve (AUC) of 0.90, Welmoed K. van Deen, MD, of the University of California, Los Angeles, and her associates wrote in Clinical Gastroenterology and Hepatology. The AUC for the ulcerative colitis index for ulcerative colitis was very similar, at 0.91. “The [mobile health indexes] are specifically designed for implementation on a mobile application, and are currently available to patients with IBD [inflammatory bowel disease] treated at the UCLA Center for IBD,” the researchers said. “Prospective, randomized studies need to assess the effect of remote monitoring on disease control, quality of life, patient satisfaction, and health care costs.”
Inspired by the lack of smartphone applications for remotely managing inflammatory bowel disease, the researchers administered comprehensive disease-specific questionnaires to 110 patients with Crohn’s disease and 109 patients with ulcerative colitis who visited the UCLA IBD center in 2013 and 2014. They compared patient-reported outcomes across 10 domains of disease activity with scores on a number of existing disease activity indexes, and used logistic regression to identify which self-reported outcomes best predicted disease activity in both Crohn’s disease and ulcerative colitis (Clin Gastroenterol Hepatol. 2015 Nov 18. doi: 10.1016/j.cgh.2015.10.035).
The resulting Crohn’s disease mobile health index asked how many liquid or “very soft” stools patients had per day, if they had abdominal pain, and how they would rate their well-being and level of disease control on scales ranging between 0 and 10. The ulcerative colitis mobile health index asked about number of stools the day before and had patients score abdominal pain, frequency of rectal bleeding, and level of disease control between 0 and 10. The researchers also validated each mobile health index in multicenter cohorts of 301 patients with Crohn’s disease and 265 patients with ulcerative colitis.
Each mobile health index detected clinical disease activity with about 90% accuracy, compared with standard measures, including the Crohn’s disease activity index and the Harvey Bradshaw index for Crohn’s disease, the partial Mayo score, the simple clinical colitis activity index, and the modified Truelove and Witts index for ulcerative colitis. But the mobile indexes detected endoscopic disease activity less accurately, with AUCs of 0.82 for ulcerative colitis and only 0.63 for Crohn’s disease. “As previously shown, ulcerative colitis clinical disease activity highly correlates with endoscopic disease activity, whereas correlation between Crohn’s disease symptoms and endoscopic findings is poor,” the researchers noted. However, both mobile indexes reliably detected changes in disease activity, varying significantly depending on whether patients were clinically improved, stable, or worse, regardless of whether they had Crohn’s disease (P = .003) or ulcerative colitis (P = .0025).
To explore intrapatient reliability, the researchers also compared initial and follow-up mobile health index results for subgroups of 40 Crohn’s disease patients tested a median of 21 hours apart, and 37 ulcerative colitis patients tested a median of 23 hours apart. In both cases, the intraclass correlation coefficient reached 0.94 (95% confidence interval, 0.89-0.97). “Cloud-based health technologies are predicted to revolutionize care delivery and patient engagement,” the investigators commented. “Patients can participate in their care by signaling meaningful health outcomes during year-round monitoring. Barriers for more widespread implementation of mobile health in inflammatory bowel disease care include policies affecting reimbursement and regulatory requirements, and privacy and security concerns.”
Genova Diagnostics provided stool collection kits and fecal calprotectin testing. The investigators had no disclosures.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Two short mobile health indexes accurately identified disease activity in Crohn’s disease and ulcerative colitis.
Major finding: Areas under the receiver operating curve (AUC) were 0.91 for Crohn’s disease and 0.90 for ulcerative colitis when compared with standard measures of clinical disease activity.
Data source: A prospective, observational study of 110 patients with Crohn’s disease and 109 patients with ulcerative colitis.
Disclosures: Genova Diagnostics provided stool collection kits and fecal calprotectin testing. The investigators had no disclosures.
Second course of rifaximin edges out placebo in IBS-D trial
Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) who responded to rifaximin but relapsed after completing treatment were significantly more likely to respond to a second course of the antibiotic than to placebo, according to a report in the December issue of Gastroenterology (2016 Aug 5. doi: 10.1053/j.gastro.2016.08.003).
A total of 38% of patients who received a second course of rifaximin met the primary endpoint in the randomized double-blinded trial, compared with 31.5% of the placebo group (P = .03), Dr. Anthony Lembo of Beth Israel Deaconess Medical Center, Boston, and his associates wrote in Gastroenterology. “Although this study had a positive outcome, questions remain regarding the role of nonsystemic antibiotics in the long term, particularly when patients with IBS-D may require years of symptom management,” they added. “Further research is needed to better understand the treatment algorithm in patients who may lose responsiveness to rifaximin.”
Rifaximin (Xifaxan) has been approved in the United States for treating IBS-D since 2015. The agent is an oral, minimally absorbed, broad-spectrum antibiotic that targets the gastrointestinal tract and has rarely been linked to “clinically relevant” antibiotic resistance, the researchers said. However, pivotal IBS-D trials had not investigated the durability of response to rifaximin or the efficacy and safety of repeat treatment, they noted. Therefore, they followed 1,074 patients with IBS-D who had responded to an open-label 2-week course of rifaximin dosed orally at 550 mg three times daily. By definition, these responders had met a combined primary endpoint that included at least a 30% decrease in abdominal pain and at least a 50% decrease in the frequency of loose stools during at least 2 of 4 weeks of follow-up.
In all, 692 (64%) responders relapsed up to 18 weeks after finishing the first rifaximin course, the investigators said. They randomly assigned 636 of these relapsers to double-blinded treatment with either placebo or a second course of rifaximin. In all, 125 of 328 patients (38.1%) in the rifaximin group again met the combined primary endpoint, compared with 97 of 308 patients (31.5%) in the placebo group (P = .03). Repeat rifaximin treatment also significantly outperformed placebo in terms of the individual abdominal pain endpoint (51% versus 42%, respectively; P = .02), but not the stool consistency endpoint (52% versus 50%).
“Adverse event rates were low and similar between groups,” the researchers said. Patients who received a second course of rifaximin most commonly developed nausea (3.7%), upper respiratory infection (3.7%), urinary tract infection (3.4%), and nasopharyngitis (3.0%). Four patients (1%) in each treatment group developed serious adverse events, none of which were deemed treatment related. One patient developed Clostridium difficile colitis 37 days after completing the second course of rifaximin. However, this patient had a past history of C. difficile infection, had tested negative for C. difficile toxins A and B at enrollment, and had completed a 10-day course of cefdinir for a urinary tract infection immediately before developing C. difficile colitis.
Salix Pharmaceuticals makes rifaximin and funded the study. Dr. Lembo and his coinvestigators disclosed ties to Salix.
Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) who responded to rifaximin but relapsed after completing treatment were significantly more likely to respond to a second course of the antibiotic than to placebo, according to a report in the December issue of Gastroenterology (2016 Aug 5. doi: 10.1053/j.gastro.2016.08.003).
A total of 38% of patients who received a second course of rifaximin met the primary endpoint in the randomized double-blinded trial, compared with 31.5% of the placebo group (P = .03), Dr. Anthony Lembo of Beth Israel Deaconess Medical Center, Boston, and his associates wrote in Gastroenterology. “Although this study had a positive outcome, questions remain regarding the role of nonsystemic antibiotics in the long term, particularly when patients with IBS-D may require years of symptom management,” they added. “Further research is needed to better understand the treatment algorithm in patients who may lose responsiveness to rifaximin.”
Rifaximin (Xifaxan) has been approved in the United States for treating IBS-D since 2015. The agent is an oral, minimally absorbed, broad-spectrum antibiotic that targets the gastrointestinal tract and has rarely been linked to “clinically relevant” antibiotic resistance, the researchers said. However, pivotal IBS-D trials had not investigated the durability of response to rifaximin or the efficacy and safety of repeat treatment, they noted. Therefore, they followed 1,074 patients with IBS-D who had responded to an open-label 2-week course of rifaximin dosed orally at 550 mg three times daily. By definition, these responders had met a combined primary endpoint that included at least a 30% decrease in abdominal pain and at least a 50% decrease in the frequency of loose stools during at least 2 of 4 weeks of follow-up.
In all, 692 (64%) responders relapsed up to 18 weeks after finishing the first rifaximin course, the investigators said. They randomly assigned 636 of these relapsers to double-blinded treatment with either placebo or a second course of rifaximin. In all, 125 of 328 patients (38.1%) in the rifaximin group again met the combined primary endpoint, compared with 97 of 308 patients (31.5%) in the placebo group (P = .03). Repeat rifaximin treatment also significantly outperformed placebo in terms of the individual abdominal pain endpoint (51% versus 42%, respectively; P = .02), but not the stool consistency endpoint (52% versus 50%).
“Adverse event rates were low and similar between groups,” the researchers said. Patients who received a second course of rifaximin most commonly developed nausea (3.7%), upper respiratory infection (3.7%), urinary tract infection (3.4%), and nasopharyngitis (3.0%). Four patients (1%) in each treatment group developed serious adverse events, none of which were deemed treatment related. One patient developed Clostridium difficile colitis 37 days after completing the second course of rifaximin. However, this patient had a past history of C. difficile infection, had tested negative for C. difficile toxins A and B at enrollment, and had completed a 10-day course of cefdinir for a urinary tract infection immediately before developing C. difficile colitis.
Salix Pharmaceuticals makes rifaximin and funded the study. Dr. Lembo and his coinvestigators disclosed ties to Salix.
Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) who responded to rifaximin but relapsed after completing treatment were significantly more likely to respond to a second course of the antibiotic than to placebo, according to a report in the December issue of Gastroenterology (2016 Aug 5. doi: 10.1053/j.gastro.2016.08.003).
A total of 38% of patients who received a second course of rifaximin met the primary endpoint in the randomized double-blinded trial, compared with 31.5% of the placebo group (P = .03), Dr. Anthony Lembo of Beth Israel Deaconess Medical Center, Boston, and his associates wrote in Gastroenterology. “Although this study had a positive outcome, questions remain regarding the role of nonsystemic antibiotics in the long term, particularly when patients with IBS-D may require years of symptom management,” they added. “Further research is needed to better understand the treatment algorithm in patients who may lose responsiveness to rifaximin.”
Rifaximin (Xifaxan) has been approved in the United States for treating IBS-D since 2015. The agent is an oral, minimally absorbed, broad-spectrum antibiotic that targets the gastrointestinal tract and has rarely been linked to “clinically relevant” antibiotic resistance, the researchers said. However, pivotal IBS-D trials had not investigated the durability of response to rifaximin or the efficacy and safety of repeat treatment, they noted. Therefore, they followed 1,074 patients with IBS-D who had responded to an open-label 2-week course of rifaximin dosed orally at 550 mg three times daily. By definition, these responders had met a combined primary endpoint that included at least a 30% decrease in abdominal pain and at least a 50% decrease in the frequency of loose stools during at least 2 of 4 weeks of follow-up.
In all, 692 (64%) responders relapsed up to 18 weeks after finishing the first rifaximin course, the investigators said. They randomly assigned 636 of these relapsers to double-blinded treatment with either placebo or a second course of rifaximin. In all, 125 of 328 patients (38.1%) in the rifaximin group again met the combined primary endpoint, compared with 97 of 308 patients (31.5%) in the placebo group (P = .03). Repeat rifaximin treatment also significantly outperformed placebo in terms of the individual abdominal pain endpoint (51% versus 42%, respectively; P = .02), but not the stool consistency endpoint (52% versus 50%).
“Adverse event rates were low and similar between groups,” the researchers said. Patients who received a second course of rifaximin most commonly developed nausea (3.7%), upper respiratory infection (3.7%), urinary tract infection (3.4%), and nasopharyngitis (3.0%). Four patients (1%) in each treatment group developed serious adverse events, none of which were deemed treatment related. One patient developed Clostridium difficile colitis 37 days after completing the second course of rifaximin. However, this patient had a past history of C. difficile infection, had tested negative for C. difficile toxins A and B at enrollment, and had completed a 10-day course of cefdinir for a urinary tract infection immediately before developing C. difficile colitis.
Salix Pharmaceuticals makes rifaximin and funded the study. Dr. Lembo and his coinvestigators disclosed ties to Salix.
FROM GASTROENTEROLOGY
Key clinical point: A second course of rifaximin may be merited in patients with diarrhea-predominant irritable bowel syndrome.
Major finding: In all, 38% of patients who received a second course of the antibiotic met the primary endpoint, compared with 31.5% of those who received placebo (P = .03),
Data source: A randomized, double-blind, phase III trial of 692 patients with IBS-D who relapsed after initially responding to a 2-week course of rifaximin.
Disclosures: Salix Pharmaceuticals, maker of rifaximin, funded the study. Dr. Lembo and his coinvestigators disclosed ties to Salix.
Yoga holds up to medications, walking for irritable bowel syndrome
Yoga may be a feasible and safe add-on therapy for patients with irritable bowel syndrome, based on a systematic review of six randomized controlled trials of 273 patients published in the December issue of Clinical Gastroenterology and Hepatology.
Yoga significantly outperformed no treatment and resembled pharmacologic therapies for IBS on measures of bowel symptoms, anxiety, and quality of life, said Dania Schumann of the University of Duisburg-Essen, Essen, Germany.
“Yoga also seems to be equally effective as a walking program in improving patient-reported outcomes,” she and her coinvestigators wrote. But “wide methodological heterogeneity” and a “mostly unclear risk of bias,” precluded a direct recommendation for yoga in IBS, they said. Nonetheless, “its practice need not be discouraged in this patient population, especially when [patients] believe that it benefits their health, quality of life, or IBS-related comorbidities.”
Experts have increasingly emphasized the role of stress, psychological disorders, and the bidirectional gut-brain axis in IBS, the reviewers noted. Because yoga had been found to cut stress and improve psychological functioning in past studies, they hypothesized that it also might improve IBS symptoms. By searching MEDLINE/Pubmed, the Cochrane Library, CAM-QUEST, CAMbase, and IndMED for studies of IBS and yoga, they identified 93 records, including six randomized controlled trials from India, the United States, and Canada. One trial defined IBS based on Rome I criteria, another used Rome II criteria, three used Rome III criteria, and the sixth trial relied solely on clinical and laboratory measures. Patients ranged in age from 14 to 44 years (median, 32 years), and most were female. They were allowed to continue their usual IBS care (Clin Gastroenterol Hepatol. 2016 Apr 22. doi: 10.1016/j.cgh.2016.04.026). Two trials compared 9-12 weeks of yoga with pharmacologic therapies. In one study, yoga and loperamide were associated with similar improvements in bowel symptoms, state anxiety, gastric motility, and other measures of autonomic reactivity. The second study found no significant differences in the colonic myoelectrical effects of yoga, placebo, and a regimen of psyllium husk, propantheline, and diazepam.
Three studies compared 4-12 weeks of Iyengar or hatha yoga with usual IBS care. Yoga outperformed standard care on measures of IBS symptoms, quality of life, psychological distress, and fatigue in two trials. The third study found a benefit for yoga after wait-listed controls joined the yoga intervention and the researchers combined their data with the other yoga group.
The sixth trial compared yoga with a walking program and found similar effects. Yoga was associated with significant improvements in abdominal pain, visceral sensitivity, and GI symptoms, while walking improved gastrointestinal symptoms, negative affect, and state anxiety. But at 6-month follow-up, walkers had fewer gastrointestinal symptoms than did the yoga group, perhaps because a walking program is easier to maintain at home, the reviewers noted.
Only one trial adequately performed adequate blinding during outcome assessments, and several others were at high risk of performance bias, reporting bias, and attrition bias, the reviewers said. The trials also did not adequately describe methods to randomize patients or conceal group allocations, and “selective reporting and high dropout rates [were] an issue,” they added.
Adverse events related to yoga included three cases of temporarily aggravated lower back pain and one fall after a participant slipped and hit his knee while in a headstand. However, only two trials assessed adverse events, the reviewers noted. “Future studies should ensure rigorous reporting of adverse events, and the correct use of terminology,” they said.
Because meditation, breathing exercises, and yoga seem to improve both stress and IBS symptoms, researchers should consider these practices when studying patients with “an increased gastrointestinal response to stress,” the reviewers concluded. “So far, the recent global guidelines of the World Gastroenterology Organization on IBS consider sufficient physical activity and relaxation techniques to be appropriate nonpharmacologic approaches.”
The reviewers did not report funding sources. They had no relevant conflicts of interest.
Yoga may be a feasible and safe add-on therapy for patients with irritable bowel syndrome, based on a systematic review of six randomized controlled trials of 273 patients published in the December issue of Clinical Gastroenterology and Hepatology.
Yoga significantly outperformed no treatment and resembled pharmacologic therapies for IBS on measures of bowel symptoms, anxiety, and quality of life, said Dania Schumann of the University of Duisburg-Essen, Essen, Germany.
“Yoga also seems to be equally effective as a walking program in improving patient-reported outcomes,” she and her coinvestigators wrote. But “wide methodological heterogeneity” and a “mostly unclear risk of bias,” precluded a direct recommendation for yoga in IBS, they said. Nonetheless, “its practice need not be discouraged in this patient population, especially when [patients] believe that it benefits their health, quality of life, or IBS-related comorbidities.”
Experts have increasingly emphasized the role of stress, psychological disorders, and the bidirectional gut-brain axis in IBS, the reviewers noted. Because yoga had been found to cut stress and improve psychological functioning in past studies, they hypothesized that it also might improve IBS symptoms. By searching MEDLINE/Pubmed, the Cochrane Library, CAM-QUEST, CAMbase, and IndMED for studies of IBS and yoga, they identified 93 records, including six randomized controlled trials from India, the United States, and Canada. One trial defined IBS based on Rome I criteria, another used Rome II criteria, three used Rome III criteria, and the sixth trial relied solely on clinical and laboratory measures. Patients ranged in age from 14 to 44 years (median, 32 years), and most were female. They were allowed to continue their usual IBS care (Clin Gastroenterol Hepatol. 2016 Apr 22. doi: 10.1016/j.cgh.2016.04.026). Two trials compared 9-12 weeks of yoga with pharmacologic therapies. In one study, yoga and loperamide were associated with similar improvements in bowel symptoms, state anxiety, gastric motility, and other measures of autonomic reactivity. The second study found no significant differences in the colonic myoelectrical effects of yoga, placebo, and a regimen of psyllium husk, propantheline, and diazepam.
Three studies compared 4-12 weeks of Iyengar or hatha yoga with usual IBS care. Yoga outperformed standard care on measures of IBS symptoms, quality of life, psychological distress, and fatigue in two trials. The third study found a benefit for yoga after wait-listed controls joined the yoga intervention and the researchers combined their data with the other yoga group.
The sixth trial compared yoga with a walking program and found similar effects. Yoga was associated with significant improvements in abdominal pain, visceral sensitivity, and GI symptoms, while walking improved gastrointestinal symptoms, negative affect, and state anxiety. But at 6-month follow-up, walkers had fewer gastrointestinal symptoms than did the yoga group, perhaps because a walking program is easier to maintain at home, the reviewers noted.
Only one trial adequately performed adequate blinding during outcome assessments, and several others were at high risk of performance bias, reporting bias, and attrition bias, the reviewers said. The trials also did not adequately describe methods to randomize patients or conceal group allocations, and “selective reporting and high dropout rates [were] an issue,” they added.
Adverse events related to yoga included three cases of temporarily aggravated lower back pain and one fall after a participant slipped and hit his knee while in a headstand. However, only two trials assessed adverse events, the reviewers noted. “Future studies should ensure rigorous reporting of adverse events, and the correct use of terminology,” they said.
Because meditation, breathing exercises, and yoga seem to improve both stress and IBS symptoms, researchers should consider these practices when studying patients with “an increased gastrointestinal response to stress,” the reviewers concluded. “So far, the recent global guidelines of the World Gastroenterology Organization on IBS consider sufficient physical activity and relaxation techniques to be appropriate nonpharmacologic approaches.”
The reviewers did not report funding sources. They had no relevant conflicts of interest.
Yoga may be a feasible and safe add-on therapy for patients with irritable bowel syndrome, based on a systematic review of six randomized controlled trials of 273 patients published in the December issue of Clinical Gastroenterology and Hepatology.
Yoga significantly outperformed no treatment and resembled pharmacologic therapies for IBS on measures of bowel symptoms, anxiety, and quality of life, said Dania Schumann of the University of Duisburg-Essen, Essen, Germany.
“Yoga also seems to be equally effective as a walking program in improving patient-reported outcomes,” she and her coinvestigators wrote. But “wide methodological heterogeneity” and a “mostly unclear risk of bias,” precluded a direct recommendation for yoga in IBS, they said. Nonetheless, “its practice need not be discouraged in this patient population, especially when [patients] believe that it benefits their health, quality of life, or IBS-related comorbidities.”
Experts have increasingly emphasized the role of stress, psychological disorders, and the bidirectional gut-brain axis in IBS, the reviewers noted. Because yoga had been found to cut stress and improve psychological functioning in past studies, they hypothesized that it also might improve IBS symptoms. By searching MEDLINE/Pubmed, the Cochrane Library, CAM-QUEST, CAMbase, and IndMED for studies of IBS and yoga, they identified 93 records, including six randomized controlled trials from India, the United States, and Canada. One trial defined IBS based on Rome I criteria, another used Rome II criteria, three used Rome III criteria, and the sixth trial relied solely on clinical and laboratory measures. Patients ranged in age from 14 to 44 years (median, 32 years), and most were female. They were allowed to continue their usual IBS care (Clin Gastroenterol Hepatol. 2016 Apr 22. doi: 10.1016/j.cgh.2016.04.026). Two trials compared 9-12 weeks of yoga with pharmacologic therapies. In one study, yoga and loperamide were associated with similar improvements in bowel symptoms, state anxiety, gastric motility, and other measures of autonomic reactivity. The second study found no significant differences in the colonic myoelectrical effects of yoga, placebo, and a regimen of psyllium husk, propantheline, and diazepam.
Three studies compared 4-12 weeks of Iyengar or hatha yoga with usual IBS care. Yoga outperformed standard care on measures of IBS symptoms, quality of life, psychological distress, and fatigue in two trials. The third study found a benefit for yoga after wait-listed controls joined the yoga intervention and the researchers combined their data with the other yoga group.
The sixth trial compared yoga with a walking program and found similar effects. Yoga was associated with significant improvements in abdominal pain, visceral sensitivity, and GI symptoms, while walking improved gastrointestinal symptoms, negative affect, and state anxiety. But at 6-month follow-up, walkers had fewer gastrointestinal symptoms than did the yoga group, perhaps because a walking program is easier to maintain at home, the reviewers noted.
Only one trial adequately performed adequate blinding during outcome assessments, and several others were at high risk of performance bias, reporting bias, and attrition bias, the reviewers said. The trials also did not adequately describe methods to randomize patients or conceal group allocations, and “selective reporting and high dropout rates [were] an issue,” they added.
Adverse events related to yoga included three cases of temporarily aggravated lower back pain and one fall after a participant slipped and hit his knee while in a headstand. However, only two trials assessed adverse events, the reviewers noted. “Future studies should ensure rigorous reporting of adverse events, and the correct use of terminology,” they said.
Because meditation, breathing exercises, and yoga seem to improve both stress and IBS symptoms, researchers should consider these practices when studying patients with “an increased gastrointestinal response to stress,” the reviewers concluded. “So far, the recent global guidelines of the World Gastroenterology Organization on IBS consider sufficient physical activity and relaxation techniques to be appropriate nonpharmacologic approaches.”
The reviewers did not report funding sources. They had no relevant conflicts of interest.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
Key clinical point: Yoga may be an appropriate adjunctive therapy for patients with irritable bowel syndrome.
Major finding: Yoga outperformed no treatment on measures of gastrointestinal symptoms, anxiety, and quality of life, and was comparable to standard medications and a walking program.
Data source: A systematic review of six randomized controlled trials of 273 patients with irritable bowel syndrome.
Disclosures: The reviewers did not report funding sources. They had no relevant conflicts of interest.