Photo from Business Wire

The European Commission (EC) has extended the conditional marketing authorization for brentuximab vedotin (Adcetris®).

The drug is now approved for use in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

Brentuximab vedotin can be marketed for this indication in the member states of the European Union as well as in Norway, Liechtenstein, and Iceland.

Conditional marketing authorization from the EC is valid for 1 year and is reviewed annually.

With conditional authorization, drug developers are required to provide comprehensive data confirming a drug’s benefit-risk balance is positive. Once these data are available, a conditional marketing authorization may be converted to a standard marketing authorization.

Drugs are eligible for conditional marketing authorization if they are designated as orphan medicines, intended for use in emergency situations, or designed to treat, prevent, or diagnose seriously debilitating or life-threatening diseases.

The EC previously granted brentuximab vedotin conditional marketing authorization for the treatment of:

• Adults with CD30+ Hodgkin lymphoma who are at an increased risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT)
• Adults with relapsed or refractory CD30+ Hodgkin lymphoma after auto-HSCT or after at least 2 prior therapies when auto-HSCT or multi-agent chemotherapy is not a treatment option
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Phase 3 data

The EC’s latest authorization for brentuximab vedotin is based on data from the phase 3 ALCANZA trial.

Updated results from ALCANZA were presented at the 2017 ASH Annual Meeting in December. Results were previously presented at the 9th Annual T-cell Lymphoma Forum in January 2017 and published in The Lancet in June 2017.

The trial included 128 evaluable patients with CD30-positive CTCL who had received at least 1 prior systemic therapy.

Sixty-four patients were assigned to receive brentuximab vedotin, and 64 were assigned to receive the investigator’s choice of methotrexate or bexarotene (control arm). Patients received treatment for up to 1 year.

For the update, the median follow-up was 33.9 months.

There was a significant improvement in the rate of objective response lasting at least 4 months (ORR4) in the brentuximab vedotin arm compared to the control arm. The ORR4 was 60.9% and 7.8%, respectively (P<0.001). The complete response rate was 18.8% and 0%, respectively (P<0.001).

The median progression-free survival was 15.8 months in the brentuximab vedotin arm and 3.6 months in the control arm (hazard ratio=0.373; 95% CI, 0.245-0.569; P<0.001).

At time of analysis, 73% of patients in the brentuximab vedotin arm and 75% in the control arm had received 1 or more subsequent skin-directed or systemic therapies. The median time to next treatment was 14.2 months in the brentuximab vedotin arm and 6.1 months in the control arm (P<0.001).

Peripheral neuropathy was the most commonly reported adverse event in patients who received brentuximab vedotin. The incidence was 67% in these patients and 6% in controls.

In the brentuximab arm, 86% of patients reported resolution or improvement in peripheral neuropathy. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 and 3 patients with grade 2 events.

Photo from Business Wire

The European Commission (EC) has extended the conditional marketing authorization for brentuximab vedotin (Adcetris®).

The drug is now approved for use in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

Brentuximab vedotin can be marketed for this indication in the member states of the European Union as well as in Norway, Liechtenstein, and Iceland.

Conditional marketing authorization from the EC is valid for 1 year and is reviewed annually.

With conditional authorization, drug developers are required to provide comprehensive data confirming a drug’s benefit-risk balance is positive. Once these data are available, a conditional marketing authorization may be converted to a standard marketing authorization.

Drugs are eligible for conditional marketing authorization if they are designated as orphan medicines, intended for use in emergency situations, or designed to treat, prevent, or diagnose seriously debilitating or life-threatening diseases.

The EC previously granted brentuximab vedotin conditional marketing authorization for the treatment of:

• Adults with CD30+ Hodgkin lymphoma who are at an increased risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT)
• Adults with relapsed or refractory CD30+ Hodgkin lymphoma after auto-HSCT or after at least 2 prior therapies when auto-HSCT or multi-agent chemotherapy is not a treatment option
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Phase 3 data

The EC’s latest authorization for brentuximab vedotin is based on data from the phase 3 ALCANZA trial.

Updated results from ALCANZA were presented at the 2017 ASH Annual Meeting in December. Results were previously presented at the 9th Annual T-cell Lymphoma Forum in January 2017 and published in The Lancet in June 2017.

The trial included 128 evaluable patients with CD30-positive CTCL who had received at least 1 prior systemic therapy.

Sixty-four patients were assigned to receive brentuximab vedotin, and 64 were assigned to receive the investigator’s choice of methotrexate or bexarotene (control arm). Patients received treatment for up to 1 year.

For the update, the median follow-up was 33.9 months.

There was a significant improvement in the rate of objective response lasting at least 4 months (ORR4) in the brentuximab vedotin arm compared to the control arm. The ORR4 was 60.9% and 7.8%, respectively (P<0.001). The complete response rate was 18.8% and 0%, respectively (P<0.001).

The median progression-free survival was 15.8 months in the brentuximab vedotin arm and 3.6 months in the control arm (hazard ratio=0.373; 95% CI, 0.245-0.569; P<0.001).

At time of analysis, 73% of patients in the brentuximab vedotin arm and 75% in the control arm had received 1 or more subsequent skin-directed or systemic therapies. The median time to next treatment was 14.2 months in the brentuximab vedotin arm and 6.1 months in the control arm (P<0.001).

Peripheral neuropathy was the most commonly reported adverse event in patients who received brentuximab vedotin. The incidence was 67% in these patients and 6% in controls.

In the brentuximab arm, 86% of patients reported resolution or improvement in peripheral neuropathy. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 and 3 patients with grade 2 events.

Photo from Business Wire

The European Commission (EC) has extended the conditional marketing authorization for brentuximab vedotin (Adcetris®).

The drug is now approved for use in adults with CD30-positive cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

Brentuximab vedotin can be marketed for this indication in the member states of the European Union as well as in Norway, Liechtenstein, and Iceland.

Conditional marketing authorization from the EC is valid for 1 year and is reviewed annually.

With conditional authorization, drug developers are required to provide comprehensive data confirming a drug’s benefit-risk balance is positive. Once these data are available, a conditional marketing authorization may be converted to a standard marketing authorization.

Drugs are eligible for conditional marketing authorization if they are designated as orphan medicines, intended for use in emergency situations, or designed to treat, prevent, or diagnose seriously debilitating or life-threatening diseases.

The EC previously granted brentuximab vedotin conditional marketing authorization for the treatment of:

• Adults with CD30+ Hodgkin lymphoma who are at an increased risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT)
• Adults with relapsed or refractory CD30+ Hodgkin lymphoma after auto-HSCT or after at least 2 prior therapies when auto-HSCT or multi-agent chemotherapy is not a treatment option
• Adults with relapsed or refractory systemic anaplastic large-cell lymphoma.

Brentuximab vedotin is under joint development by Seattle Genetics and Takeda Pharmaceutical Company Limited.

Phase 3 data

The EC’s latest authorization for brentuximab vedotin is based on data from the phase 3 ALCANZA trial.

Updated results from ALCANZA were presented at the 2017 ASH Annual Meeting in December. Results were previously presented at the 9th Annual T-cell Lymphoma Forum in January 2017 and published in The Lancet in June 2017.

The trial included 128 evaluable patients with CD30-positive CTCL who had received at least 1 prior systemic therapy.

Sixty-four patients were assigned to receive brentuximab vedotin, and 64 were assigned to receive the investigator’s choice of methotrexate or bexarotene (control arm). Patients received treatment for up to 1 year.

For the update, the median follow-up was 33.9 months.

There was a significant improvement in the rate of objective response lasting at least 4 months (ORR4) in the brentuximab vedotin arm compared to the control arm. The ORR4 was 60.9% and 7.8%, respectively (P<0.001). The complete response rate was 18.8% and 0%, respectively (P<0.001).

The median progression-free survival was 15.8 months in the brentuximab vedotin arm and 3.6 months in the control arm (hazard ratio=0.373; 95% CI, 0.245-0.569; P<0.001).

At time of analysis, 73% of patients in the brentuximab vedotin arm and 75% in the control arm had received 1 or more subsequent skin-directed or systemic therapies. The median time to next treatment was 14.2 months in the brentuximab vedotin arm and 6.1 months in the control arm (P<0.001).

Peripheral neuropathy was the most commonly reported adverse event in patients who received brentuximab vedotin. The incidence was 67% in these patients and 6% in controls.

In the brentuximab arm, 86% of patients reported resolution or improvement in peripheral neuropathy. Eighteen patients had ongoing peripheral neuropathy events, including 15 patients with grade 1 and 3 patients with grade 2 events.

Photo courtesy of GSK

Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.

The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.

Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.

And Novartis will continue to market ofatumumab for CLL in the US.

“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.

Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.

The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.

About ofatumumab

Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.

In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.

Other approved indications for ofatumumab in the European Union include:

• In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
• In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.

Other approved indications for ofatumumab in the US include:

• In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
• In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
• For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
  

Photo courtesy of GSK

Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.

The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.

Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.

And Novartis will continue to market ofatumumab for CLL in the US.

“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.

Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.

The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.

About ofatumumab

Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.

In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.

Other approved indications for ofatumumab in the European Union include:

• In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
• In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.

Other approved indications for ofatumumab in the US include:

• In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
• In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
• For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
  

Photo courtesy of GSK

Novartis is planning to stop marketing ofatumumab (Arzerra®) outside the US, but the drug will still be available for certain patients.

The company plans to work with regulatory authorities to establish compassionate use programs for chronic lymphocytic leukemia (CLL) patients outside the US who are currently receiving ofatumumab.

Patients accessing these programs will be offered continued treatment with ofatumumab for as long as they benefit from it, free of charge.

And Novartis will continue to market ofatumumab for CLL in the US.

“Novartis’s intention to transition Arzerra to compassionate use programs in the non-US markets reflects the fact that many more drugs have become available for CLL over the last 5 years and that there is a low number of patients using Arzerra outside of the US market,” said Jan van de Winkel, PhD, chief executive officer of Genmab.

Ofatumumab is marketed under a collaboration agreement between Genmab and Novartis.

Because Novartis has decided to pull ofatumumab from non-US markets, the company will pay Genmab a lump sum of $50 million (USD) for lost potential milestones and royalties. Royalties will continue to be earned on net sales of the drug.

Novartis intends to start the transition to compassionate use programs as soon as the company and regulatory authorities have agreed to a plan.

The two phase 3 studies of ofatumumab in relapsing multiple sclerosis and the study in indolent non-Hodgkin lymphoma will not be affected by this change. All 3 trials will continue.

About ofatumumab

Ofatumumab is a monoclonal antibody designed to target CD20 on the surface of CLL cells and normal B lymphocytes.

In more than 60 countries worldwide, including the US and European Union member countries, ofatumumab is approved as monotherapy for CLL patients who are refractory to treatment with fludarabine and alemtuzumab.

Other approved indications for ofatumumab in the European Union include:

• In combination with chlorambucil or bendamustine to treat CLL patients who have not received prior therapy and are not eligible for fludarabine-based therapy
• In combination with fludarabine and cyclophosphamide to treat adults with relapsed CLL.

Other approved indications for ofatumumab in the US include:

• In combination with chlorambucil to treat previously untreated CLL patients for whom fludarabine-based therapy is considered inappropriate
• In combination with fludarabine and cyclophosphamide to treat patients with relapsed CLL
• For extended treatment of patients who are in complete or partial response after at least 2 lines of therapy for recurrent or progressive CLL.
  

Photo by Steven Harbour

A group of US health systems is planning to form a not-for-profit generic drug company with the goal of ending drug shortages and reducing prices for patients.

The company will either directly manufacture generic drugs or subcontract manufacturing to organizations it deems reputable.

“For people in the United States, there is a dangerous gap today between the demand and supply of affordable prescription drugs,” said Richard J. Gilfillan, MD, chief executive officer of Trinity Health, one of the health systems involved in this project.

“If the only way to provide our communities with affordable drugs is to produce them ourselves, then that is what we will do. We look forward to more healthcare systems around the country joining this people-centered effort.”

The organizations involved in this project include Intermountain Healthcare, Ascension, SSM Health, and Trinity Health, as well as the US Department of Veterans Affairs (although the department has not provided financial support for the project).

The 5 organizations represent more than 450 hospitals around the US, and other health systems are set to join the initiative as well.

“It’s an ambitious plan, but healthcare systems are in the best position to fix the problems in the generic drug market,” said Marc Harrison, MD, president and chief executive officer of Intermountain Healthcare.

“We witness, on a daily basis, how shortages of essential generic medications or egregious cost increases for those same drugs affect our patients. We are confident we can improve the situation for our patients by bringing much-needed competition to the generic drug market.”

The formation of this not-for-profit generic drug company will be guided by an advisory committee, which will include:

• Madhu Balachandran, retired executive vice-president of Global Operations, Amgen
• Don Berwick, MD, president emeritus and senior fellow, Institute for Healthcare Improvement; former Centers for Medicare & Medicaid Services administrator
• Clayton Christensen, professor at Harvard Business School and founder of Innosight
• Bob Kerrey, managing director, Allen & Company; former Nebraska governor and US senator
• Martin VanTrieste, retired senior vice-president and chief quality officer, Amgen
• Senior-level leaders from the organizations founding the company.
  

Photo by Steven Harbour

A group of US health systems is planning to form a not-for-profit generic drug company with the goal of ending drug shortages and reducing prices for patients.

The company will either directly manufacture generic drugs or subcontract manufacturing to organizations it deems reputable.

“For people in the United States, there is a dangerous gap today between the demand and supply of affordable prescription drugs,” said Richard J. Gilfillan, MD, chief executive officer of Trinity Health, one of the health systems involved in this project.

“If the only way to provide our communities with affordable drugs is to produce them ourselves, then that is what we will do. We look forward to more healthcare systems around the country joining this people-centered effort.”

The organizations involved in this project include Intermountain Healthcare, Ascension, SSM Health, and Trinity Health, as well as the US Department of Veterans Affairs (although the department has not provided financial support for the project).

The 5 organizations represent more than 450 hospitals around the US, and other health systems are set to join the initiative as well.

“It’s an ambitious plan, but healthcare systems are in the best position to fix the problems in the generic drug market,” said Marc Harrison, MD, president and chief executive officer of Intermountain Healthcare.

“We witness, on a daily basis, how shortages of essential generic medications or egregious cost increases for those same drugs affect our patients. We are confident we can improve the situation for our patients by bringing much-needed competition to the generic drug market.”

The formation of this not-for-profit generic drug company will be guided by an advisory committee, which will include:

• Madhu Balachandran, retired executive vice-president of Global Operations, Amgen
• Don Berwick, MD, president emeritus and senior fellow, Institute for Healthcare Improvement; former Centers for Medicare & Medicaid Services administrator
• Clayton Christensen, professor at Harvard Business School and founder of Innosight
• Bob Kerrey, managing director, Allen & Company; former Nebraska governor and US senator
• Martin VanTrieste, retired senior vice-president and chief quality officer, Amgen
• Senior-level leaders from the organizations founding the company.
  

Photo by Steven Harbour

A group of US health systems is planning to form a not-for-profit generic drug company with the goal of ending drug shortages and reducing prices for patients.

The company will either directly manufacture generic drugs or subcontract manufacturing to organizations it deems reputable.

“For people in the United States, there is a dangerous gap today between the demand and supply of affordable prescription drugs,” said Richard J. Gilfillan, MD, chief executive officer of Trinity Health, one of the health systems involved in this project.

“If the only way to provide our communities with affordable drugs is to produce them ourselves, then that is what we will do. We look forward to more healthcare systems around the country joining this people-centered effort.”

The organizations involved in this project include Intermountain Healthcare, Ascension, SSM Health, and Trinity Health, as well as the US Department of Veterans Affairs (although the department has not provided financial support for the project).

The 5 organizations represent more than 450 hospitals around the US, and other health systems are set to join the initiative as well.

“It’s an ambitious plan, but healthcare systems are in the best position to fix the problems in the generic drug market,” said Marc Harrison, MD, president and chief executive officer of Intermountain Healthcare.

“We witness, on a daily basis, how shortages of essential generic medications or egregious cost increases for those same drugs affect our patients. We are confident we can improve the situation for our patients by bringing much-needed competition to the generic drug market.”

The formation of this not-for-profit generic drug company will be guided by an advisory committee, which will include:

• Madhu Balachandran, retired executive vice-president of Global Operations, Amgen
• Don Berwick, MD, president emeritus and senior fellow, Institute for Healthcare Improvement; former Centers for Medicare & Medicaid Services administrator
• Clayton Christensen, professor at Harvard Business School and founder of Innosight
• Bob Kerrey, managing director, Allen & Company; former Nebraska governor and US senator
• Martin VanTrieste, retired senior vice-president and chief quality officer, Amgen
• Senior-level leaders from the organizations founding the company.
  

Clinical question: What percent of inpatient health care spending by hospitalists can be attributed to defensive medicine?

Background: Defensive medicine contributes an estimated $45 billion to annual U.S. health care expenditures. The prevalence of defensive medicine among hospitalists is unknown.

Clinical question: What percent of inpatient health care spending by hospitalists can be attributed to defensive medicine?

Background: Defensive medicine contributes an estimated $45 billion to annual U.S. health care expenditures. The prevalence of defensive medicine among hospitalists is unknown.

Clinical question: What percent of inpatient health care spending by hospitalists can be attributed to defensive medicine?

Background: Defensive medicine contributes an estimated $45 billion to annual U.S. health care expenditures. The prevalence of defensive medicine among hospitalists is unknown.

Eradicating chronic hepatitis C virus (HCV) infection led to significant decreases in liver stiffness in a systematic review and meta-analysis of nearly 3,000 patients.

Mean liver stiffness fell by 4.1 kPa (kilopascals) (95% confidence interval, 3.3-4.9 kPa) 12 or more months after patients achieved sustained virologic response to treatment, but did not significantly change in patients who did not achieve SVR, reported Siddharth Singh, MD, of the University of San Diego, La Jolla, Calif., and his associates in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.038). The results were especially striking among patients who received direct-acting antiviral agents (DAAs) or who had high baseline levels of inflammation, the investigators added.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Based on these findings, about 47% of patients with advanced fibrosis or cirrhosis at baseline will drop below 9.5 kPa after achieving SVR, they reported. “With this decline in liver stiffness, it is conceivable that risk of liver-related complications would decrease, particularly in patients without cirrhosis,” they added. “Future research is warranted on the impact of magnitude and kinetics of decline in liver stiffness on improvement in liver-related outcomes.”

Eradicating HCV infection was known to decrease liver stiffness, but the magnitude of decline was not well understood. Therefore, the reviewers searched the literature through October 2016 for studies of HCV-infected adults who underwent liver stiffness measurement by vibration-controlled transient elastography before and at least once after completing HCV treatment. All studies also included data on median liver stiffness among patients who did and did not achieve SVR. The search identified 23 observational studies and one post hoc analysis of a randomized controlled trial, for a total of 2,934 patients, of whom 2,214 achieved SVR.

Among patients who achieved SVR, mean liver stiffness dropped by 2.4 kPa at the end of treatment (95% CI, 1.7-3.0 kPa), by 3.1 kPa 1-6 months later (95% CI, 1.6-4.7 kPa), and by 3.2 kPa 6-12 months after completing treatment (90% CI, 2.6-3.9 kPa). A year or more after finishing treatment, patients who achieved SVR had a 28% median decrease in liver stiffness (interquartile range, 22%-35%). However, liver stiffness did not significantly change among patients who did not achieve SVR, the reviewers reported.

Mean liver stiffness declined significantly more among patients who received DAAs (4.5 kPa) than among recipients of interferon-based regimens (2.6 kPa; P = .03). However, studies of DAAs included patients with greater liver stiffness at baseline, which could at least partially explain this discrepancy, the investigators said. Baseline cirrhosis also was associated with a greater decline in liver stiffness (mean, 5.1 kPa, vs. 2.8 kPa in patients without cirrhosis; P = .02), as was high baseline alanine aminotransferase level (P less than .01). Among patients whose baseline liver stiffness measurement exceeded 9.5 kPa, 47% had their liver stiffness drop to less than 9.5 kPa after achieving SVR.

Coinfection with HIV did not significantly alter the magnitude of decline in liver stiffness 6-12 months after treatment in patients who achieved SVR, the reviewers noted. “[Follow-up] assessment after SVR was relatively short; hence, long-term evolution of liver stiffness after antiviral therapy and impact of decline in liver stiffness on patient clinical outcomes could not be ascertained,” they wrote. The studies also did not consistently assess potential confounders such as nonalcoholic fatty liver disease, diabetes, and alcohol consumption.

One reviewer disclosed funding from the National Institutes of Health/National Library of Medicine. None had conflicts of interest.

Eradicating chronic hepatitis C virus (HCV) infection led to significant decreases in liver stiffness in a systematic review and meta-analysis of nearly 3,000 patients.

Mean liver stiffness fell by 4.1 kPa (kilopascals) (95% confidence interval, 3.3-4.9 kPa) 12 or more months after patients achieved sustained virologic response to treatment, but did not significantly change in patients who did not achieve SVR, reported Siddharth Singh, MD, of the University of San Diego, La Jolla, Calif., and his associates in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.038). The results were especially striking among patients who received direct-acting antiviral agents (DAAs) or who had high baseline levels of inflammation, the investigators added.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Based on these findings, about 47% of patients with advanced fibrosis or cirrhosis at baseline will drop below 9.5 kPa after achieving SVR, they reported. “With this decline in liver stiffness, it is conceivable that risk of liver-related complications would decrease, particularly in patients without cirrhosis,” they added. “Future research is warranted on the impact of magnitude and kinetics of decline in liver stiffness on improvement in liver-related outcomes.”

Eradicating HCV infection was known to decrease liver stiffness, but the magnitude of decline was not well understood. Therefore, the reviewers searched the literature through October 2016 for studies of HCV-infected adults who underwent liver stiffness measurement by vibration-controlled transient elastography before and at least once after completing HCV treatment. All studies also included data on median liver stiffness among patients who did and did not achieve SVR. The search identified 23 observational studies and one post hoc analysis of a randomized controlled trial, for a total of 2,934 patients, of whom 2,214 achieved SVR.

Among patients who achieved SVR, mean liver stiffness dropped by 2.4 kPa at the end of treatment (95% CI, 1.7-3.0 kPa), by 3.1 kPa 1-6 months later (95% CI, 1.6-4.7 kPa), and by 3.2 kPa 6-12 months after completing treatment (90% CI, 2.6-3.9 kPa). A year or more after finishing treatment, patients who achieved SVR had a 28% median decrease in liver stiffness (interquartile range, 22%-35%). However, liver stiffness did not significantly change among patients who did not achieve SVR, the reviewers reported.

Mean liver stiffness declined significantly more among patients who received DAAs (4.5 kPa) than among recipients of interferon-based regimens (2.6 kPa; P = .03). However, studies of DAAs included patients with greater liver stiffness at baseline, which could at least partially explain this discrepancy, the investigators said. Baseline cirrhosis also was associated with a greater decline in liver stiffness (mean, 5.1 kPa, vs. 2.8 kPa in patients without cirrhosis; P = .02), as was high baseline alanine aminotransferase level (P less than .01). Among patients whose baseline liver stiffness measurement exceeded 9.5 kPa, 47% had their liver stiffness drop to less than 9.5 kPa after achieving SVR.

Coinfection with HIV did not significantly alter the magnitude of decline in liver stiffness 6-12 months after treatment in patients who achieved SVR, the reviewers noted. “[Follow-up] assessment after SVR was relatively short; hence, long-term evolution of liver stiffness after antiviral therapy and impact of decline in liver stiffness on patient clinical outcomes could not be ascertained,” they wrote. The studies also did not consistently assess potential confounders such as nonalcoholic fatty liver disease, diabetes, and alcohol consumption.

One reviewer disclosed funding from the National Institutes of Health/National Library of Medicine. None had conflicts of interest.

Eradicating chronic hepatitis C virus (HCV) infection led to significant decreases in liver stiffness in a systematic review and meta-analysis of nearly 3,000 patients.

Mean liver stiffness fell by 4.1 kPa (kilopascals) (95% confidence interval, 3.3-4.9 kPa) 12 or more months after patients achieved sustained virologic response to treatment, but did not significantly change in patients who did not achieve SVR, reported Siddharth Singh, MD, of the University of San Diego, La Jolla, Calif., and his associates in the January issue of Clinical Gastroenterology and Hepatology (doi: 10.1016/j.cgh.2017.04.038). The results were especially striking among patients who received direct-acting antiviral agents (DAAs) or who had high baseline levels of inflammation, the investigators added.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

Based on these findings, about 47% of patients with advanced fibrosis or cirrhosis at baseline will drop below 9.5 kPa after achieving SVR, they reported. “With this decline in liver stiffness, it is conceivable that risk of liver-related complications would decrease, particularly in patients without cirrhosis,” they added. “Future research is warranted on the impact of magnitude and kinetics of decline in liver stiffness on improvement in liver-related outcomes.”

Eradicating HCV infection was known to decrease liver stiffness, but the magnitude of decline was not well understood. Therefore, the reviewers searched the literature through October 2016 for studies of HCV-infected adults who underwent liver stiffness measurement by vibration-controlled transient elastography before and at least once after completing HCV treatment. All studies also included data on median liver stiffness among patients who did and did not achieve SVR. The search identified 23 observational studies and one post hoc analysis of a randomized controlled trial, for a total of 2,934 patients, of whom 2,214 achieved SVR.

Among patients who achieved SVR, mean liver stiffness dropped by 2.4 kPa at the end of treatment (95% CI, 1.7-3.0 kPa), by 3.1 kPa 1-6 months later (95% CI, 1.6-4.7 kPa), and by 3.2 kPa 6-12 months after completing treatment (90% CI, 2.6-3.9 kPa). A year or more after finishing treatment, patients who achieved SVR had a 28% median decrease in liver stiffness (interquartile range, 22%-35%). However, liver stiffness did not significantly change among patients who did not achieve SVR, the reviewers reported.

Mean liver stiffness declined significantly more among patients who received DAAs (4.5 kPa) than among recipients of interferon-based regimens (2.6 kPa; P = .03). However, studies of DAAs included patients with greater liver stiffness at baseline, which could at least partially explain this discrepancy, the investigators said. Baseline cirrhosis also was associated with a greater decline in liver stiffness (mean, 5.1 kPa, vs. 2.8 kPa in patients without cirrhosis; P = .02), as was high baseline alanine aminotransferase level (P less than .01). Among patients whose baseline liver stiffness measurement exceeded 9.5 kPa, 47% had their liver stiffness drop to less than 9.5 kPa after achieving SVR.

Coinfection with HIV did not significantly alter the magnitude of decline in liver stiffness 6-12 months after treatment in patients who achieved SVR, the reviewers noted. “[Follow-up] assessment after SVR was relatively short; hence, long-term evolution of liver stiffness after antiviral therapy and impact of decline in liver stiffness on patient clinical outcomes could not be ascertained,” they wrote. The studies also did not consistently assess potential confounders such as nonalcoholic fatty liver disease, diabetes, and alcohol consumption.

One reviewer disclosed funding from the National Institutes of Health/National Library of Medicine. None had conflicts of interest.

GI & Hepatology News is one of the most widely read publications focused on the gastroenterology community and is the official newspaper of the AGA. The New Gastroenterologist is the AGA publication targeted to trainees and early career physicians. Recognizing the strength of both digital and print communication, the AGA has consolidated its communication media.

John I. Allen, MD, MBA, AGAF
Editor in Chief of GI & Hepatology News

When The New Gastroenterologist debuted almost 3 years ago, it provided a mechanism for the AGA to condense and disseminate information in a single publication for those of us in training or in the early stages of our careers. Since then, The New Gastroenterologist has become a valuable resource for the AGA community and beyond. It is with great excitement that in 2018, The New Gastroenterologist will switch to a primarily digital format. Content will be distributed in quarterly e-newsletters, which will allow for easier distribution via social media. This will allow for the creation of a website archive of past articles that can be easily queried and accessed. Additionally, The New Gastroenterologist will debut an “In Focus” series of concise updates on pertinent topics in our field. These In Focus articles will be published on a quarterly basis in GI & Hepatology News and will undoubtedly be practical and informative features that will be of interest to all AGA members, regardless of their career stage. The first In Focus article, which appears in this issue of GI & Hepatology News, is written by Nitin Ahuja, MD, and James Reynolds, MD, and provides an enlightening overview of the evaluation and management of chronic constipation. I hope that everyone enjoys this new format of The New Gastroenterologist. As always, if you have any feedback, have interest in contributing, or have ideas that you would like to hear about, please contact me (bryson.katona@uphs.upenn.edu) or Managing Editor Ryan Farrell (rfarrell@gastro.org).

Bryson W. Katona, MD, PhD
Editor in Chief of The New Gastroenterologist

GI & Hepatology News is one of the most widely read publications focused on the gastroenterology community and is the official newspaper of the AGA. The New Gastroenterologist is the AGA publication targeted to trainees and early career physicians. Recognizing the strength of both digital and print communication, the AGA has consolidated its communication media.

John I. Allen, MD, MBA, AGAF
Editor in Chief of GI & Hepatology News

When The New Gastroenterologist debuted almost 3 years ago, it provided a mechanism for the AGA to condense and disseminate information in a single publication for those of us in training or in the early stages of our careers. Since then, The New Gastroenterologist has become a valuable resource for the AGA community and beyond. It is with great excitement that in 2018, The New Gastroenterologist will switch to a primarily digital format. Content will be distributed in quarterly e-newsletters, which will allow for easier distribution via social media. This will allow for the creation of a website archive of past articles that can be easily queried and accessed. Additionally, The New Gastroenterologist will debut an “In Focus” series of concise updates on pertinent topics in our field. These In Focus articles will be published on a quarterly basis in GI & Hepatology News and will undoubtedly be practical and informative features that will be of interest to all AGA members, regardless of their career stage. The first In Focus article, which appears in this issue of GI & Hepatology News, is written by Nitin Ahuja, MD, and James Reynolds, MD, and provides an enlightening overview of the evaluation and management of chronic constipation. I hope that everyone enjoys this new format of The New Gastroenterologist. As always, if you have any feedback, have interest in contributing, or have ideas that you would like to hear about, please contact me (bryson.katona@uphs.upenn.edu) or Managing Editor Ryan Farrell (rfarrell@gastro.org).

Bryson W. Katona, MD, PhD
Editor in Chief of The New Gastroenterologist

GI & Hepatology News is one of the most widely read publications focused on the gastroenterology community and is the official newspaper of the AGA. The New Gastroenterologist is the AGA publication targeted to trainees and early career physicians. Recognizing the strength of both digital and print communication, the AGA has consolidated its communication media.

John I. Allen, MD, MBA, AGAF
Editor in Chief of GI & Hepatology News

When The New Gastroenterologist debuted almost 3 years ago, it provided a mechanism for the AGA to condense and disseminate information in a single publication for those of us in training or in the early stages of our careers. Since then, The New Gastroenterologist has become a valuable resource for the AGA community and beyond. It is with great excitement that in 2018, The New Gastroenterologist will switch to a primarily digital format. Content will be distributed in quarterly e-newsletters, which will allow for easier distribution via social media. This will allow for the creation of a website archive of past articles that can be easily queried and accessed. Additionally, The New Gastroenterologist will debut an “In Focus” series of concise updates on pertinent topics in our field. These In Focus articles will be published on a quarterly basis in GI & Hepatology News and will undoubtedly be practical and informative features that will be of interest to all AGA members, regardless of their career stage. The first In Focus article, which appears in this issue of GI & Hepatology News, is written by Nitin Ahuja, MD, and James Reynolds, MD, and provides an enlightening overview of the evaluation and management of chronic constipation. I hope that everyone enjoys this new format of The New Gastroenterologist. As always, if you have any feedback, have interest in contributing, or have ideas that you would like to hear about, please contact me (bryson.katona@uphs.upenn.edu) or Managing Editor Ryan Farrell (rfarrell@gastro.org).

Bryson W. Katona, MD, PhD
Editor in Chief of The New Gastroenterologist

WASHINGTON, DC—Smartphone videos may help to support the clinical diagnosis of psychogenic nonepileptic seizures (PNES), according to research presented at the 71st Annual Meeting of the American Epilepsy Society. However, smartphone videos do not replace the need for video-EEG monitoring, researchers noted. “Smartphone videos are a complementary addition to medical history and physical examinations in the outpatient epilepsy clinic and can help triage hospital admission for video EEG-monitoring,” said William O. Tatum, DO, Professor of Neurology at the Mayo Clinic College of Medicine in Jacksonville, Florida, and colleagues. “Most patients bringing smart videos to the clinic are ultimately diagnosed with PNES and nearly 70% are women.”

Video-EEG monitoring is the standard technique for a definitive diagnosis in patients with suspected seizures. Approximately 20% to 30% of patients admitted to the video-EEG monitoring unit are misdiagnosed with epilepsy, however. In addition, expertise availability, cost, and resource utilization of video-EEG monitoring is limited. Patient-generated videos can potentially address these limitations.

A Multicenter Blinded Trial

Dr. Tatum and colleagues conducted a prospective, multicenter, blinded trial to determine the usefulness of outpatient smartphone videos in epilepsy evaluation. Investigators evaluated 41 consecutive patients with uncontrolled seizures (13 participants were male; mean age was 43.7). Patients were excluded if they were younger than 18, had an incomplete medical history and physical examination, had an atypical event, had an inadequate smartphone video, had an unconfirmed video-EEG monitoring diagnosis, or if they did not consent.

Medical history and physical examinations, smartphone videos, and video-EEG monitoring were performed from July 2014 to November 2017. Treating physicians reached a final clinical diagnosis of epilepsy, PNES, or physiologic non-epileptic events using a degree of certainty (scale: 0–10). Ten epileptologists and eight general neurology residents without a special interest in epilepsy were surveyed for a blinded smartphone video diagnosis.

Researchers shared data via HIPPA-protected data transfer utilizing web-based software. The history and physical exams, smartphone videos, and video-EEG monitoring results were obtained using survey forms and were then compared. Finally, sensitivity, specificity, and positive and negative predictive values were analyzed.

Most Smartphone Videos Showed Nonconvulsive Seizures

Epileptologists performed 310 smartphone video reads and residents performed 230 smartphone video reads. Smartphone videos were reviewed in 2.15 minutes compared with 60 minutes for medical history and physicals and 2.54 days for video-EEG monitoring. Most semiology was convulsive and most epilepsy was nonconvulsive. Physicians made a final diagnosis of PNES in 26 patients, epilepsy in 11 patients, physiologic non-epileptic events in three patients, and a PNES with physiologic non-epileptic events in one patient. Medical history and physical examination predicted a definitive diagnosis by video-EEG monitoring in 31 patients.

The median correct response for a smart phone video was 71.4% for epileptologists and 66.7% for residents. The level of confidence was similar between experts and residents, but those who made a correct diagnosis were slightly more confident. Using a level of confidence of at least five, 78% of epileptologists provided correct identification versus 68% of residents. “This suggests that a gap exists in training relative to viewing semiology for diagnostic implications and supports the ongoing need for education in patients with ’events‘”, said Dr. Tatum and colleagues.

The overall quality of smartphone videos was considered adequate for interpretation in 78% of patients. Inter-subject differences were present mainly based upon technical limitations as opposed to video quality. The primary technical limitation was lack of focus on the area of the interest. Researchers concluded that the “secure uploading, exchange, and analysis of smartphone video data in patients with paroxysmal neurological events is feasible.” No safety concerns or complications of taking smartphone videos were reported.

—Erica Tricarico

WASHINGTON, DC—Smartphone videos may help to support the clinical diagnosis of psychogenic nonepileptic seizures (PNES), according to research presented at the 71st Annual Meeting of the American Epilepsy Society. However, smartphone videos do not replace the need for video-EEG monitoring, researchers noted. “Smartphone videos are a complementary addition to medical history and physical examinations in the outpatient epilepsy clinic and can help triage hospital admission for video EEG-monitoring,” said William O. Tatum, DO, Professor of Neurology at the Mayo Clinic College of Medicine in Jacksonville, Florida, and colleagues. “Most patients bringing smart videos to the clinic are ultimately diagnosed with PNES and nearly 70% are women.”

Video-EEG monitoring is the standard technique for a definitive diagnosis in patients with suspected seizures. Approximately 20% to 30% of patients admitted to the video-EEG monitoring unit are misdiagnosed with epilepsy, however. In addition, expertise availability, cost, and resource utilization of video-EEG monitoring is limited. Patient-generated videos can potentially address these limitations.

A Multicenter Blinded Trial

Dr. Tatum and colleagues conducted a prospective, multicenter, blinded trial to determine the usefulness of outpatient smartphone videos in epilepsy evaluation. Investigators evaluated 41 consecutive patients with uncontrolled seizures (13 participants were male; mean age was 43.7). Patients were excluded if they were younger than 18, had an incomplete medical history and physical examination, had an atypical event, had an inadequate smartphone video, had an unconfirmed video-EEG monitoring diagnosis, or if they did not consent.

Medical history and physical examinations, smartphone videos, and video-EEG monitoring were performed from July 2014 to November 2017. Treating physicians reached a final clinical diagnosis of epilepsy, PNES, or physiologic non-epileptic events using a degree of certainty (scale: 0–10). Ten epileptologists and eight general neurology residents without a special interest in epilepsy were surveyed for a blinded smartphone video diagnosis.

Researchers shared data via HIPPA-protected data transfer utilizing web-based software. The history and physical exams, smartphone videos, and video-EEG monitoring results were obtained using survey forms and were then compared. Finally, sensitivity, specificity, and positive and negative predictive values were analyzed.

Most Smartphone Videos Showed Nonconvulsive Seizures

Epileptologists performed 310 smartphone video reads and residents performed 230 smartphone video reads. Smartphone videos were reviewed in 2.15 minutes compared with 60 minutes for medical history and physicals and 2.54 days for video-EEG monitoring. Most semiology was convulsive and most epilepsy was nonconvulsive. Physicians made a final diagnosis of PNES in 26 patients, epilepsy in 11 patients, physiologic non-epileptic events in three patients, and a PNES with physiologic non-epileptic events in one patient. Medical history and physical examination predicted a definitive diagnosis by video-EEG monitoring in 31 patients.

The median correct response for a smart phone video was 71.4% for epileptologists and 66.7% for residents. The level of confidence was similar between experts and residents, but those who made a correct diagnosis were slightly more confident. Using a level of confidence of at least five, 78% of epileptologists provided correct identification versus 68% of residents. “This suggests that a gap exists in training relative to viewing semiology for diagnostic implications and supports the ongoing need for education in patients with ’events‘”, said Dr. Tatum and colleagues.

The overall quality of smartphone videos was considered adequate for interpretation in 78% of patients. Inter-subject differences were present mainly based upon technical limitations as opposed to video quality. The primary technical limitation was lack of focus on the area of the interest. Researchers concluded that the “secure uploading, exchange, and analysis of smartphone video data in patients with paroxysmal neurological events is feasible.” No safety concerns or complications of taking smartphone videos were reported.

—Erica Tricarico

WASHINGTON, DC—Smartphone videos may help to support the clinical diagnosis of psychogenic nonepileptic seizures (PNES), according to research presented at the 71st Annual Meeting of the American Epilepsy Society. However, smartphone videos do not replace the need for video-EEG monitoring, researchers noted. “Smartphone videos are a complementary addition to medical history and physical examinations in the outpatient epilepsy clinic and can help triage hospital admission for video EEG-monitoring,” said William O. Tatum, DO, Professor of Neurology at the Mayo Clinic College of Medicine in Jacksonville, Florida, and colleagues. “Most patients bringing smart videos to the clinic are ultimately diagnosed with PNES and nearly 70% are women.”

Video-EEG monitoring is the standard technique for a definitive diagnosis in patients with suspected seizures. Approximately 20% to 30% of patients admitted to the video-EEG monitoring unit are misdiagnosed with epilepsy, however. In addition, expertise availability, cost, and resource utilization of video-EEG monitoring is limited. Patient-generated videos can potentially address these limitations.

A Multicenter Blinded Trial

Dr. Tatum and colleagues conducted a prospective, multicenter, blinded trial to determine the usefulness of outpatient smartphone videos in epilepsy evaluation. Investigators evaluated 41 consecutive patients with uncontrolled seizures (13 participants were male; mean age was 43.7). Patients were excluded if they were younger than 18, had an incomplete medical history and physical examination, had an atypical event, had an inadequate smartphone video, had an unconfirmed video-EEG monitoring diagnosis, or if they did not consent.

Medical history and physical examinations, smartphone videos, and video-EEG monitoring were performed from July 2014 to November 2017. Treating physicians reached a final clinical diagnosis of epilepsy, PNES, or physiologic non-epileptic events using a degree of certainty (scale: 0–10). Ten epileptologists and eight general neurology residents without a special interest in epilepsy were surveyed for a blinded smartphone video diagnosis.

Researchers shared data via HIPPA-protected data transfer utilizing web-based software. The history and physical exams, smartphone videos, and video-EEG monitoring results were obtained using survey forms and were then compared. Finally, sensitivity, specificity, and positive and negative predictive values were analyzed.

Most Smartphone Videos Showed Nonconvulsive Seizures

Epileptologists performed 310 smartphone video reads and residents performed 230 smartphone video reads. Smartphone videos were reviewed in 2.15 minutes compared with 60 minutes for medical history and physicals and 2.54 days for video-EEG monitoring. Most semiology was convulsive and most epilepsy was nonconvulsive. Physicians made a final diagnosis of PNES in 26 patients, epilepsy in 11 patients, physiologic non-epileptic events in three patients, and a PNES with physiologic non-epileptic events in one patient. Medical history and physical examination predicted a definitive diagnosis by video-EEG monitoring in 31 patients.

The median correct response for a smart phone video was 71.4% for epileptologists and 66.7% for residents. The level of confidence was similar between experts and residents, but those who made a correct diagnosis were slightly more confident. Using a level of confidence of at least five, 78% of epileptologists provided correct identification versus 68% of residents. “This suggests that a gap exists in training relative to viewing semiology for diagnostic implications and supports the ongoing need for education in patients with ’events‘”, said Dr. Tatum and colleagues.

The overall quality of smartphone videos was considered adequate for interpretation in 78% of patients. Inter-subject differences were present mainly based upon technical limitations as opposed to video quality. The primary technical limitation was lack of focus on the area of the interest. Researchers concluded that the “secure uploading, exchange, and analysis of smartphone video data in patients with paroxysmal neurological events is feasible.” No safety concerns or complications of taking smartphone videos were reported.

—Erica Tricarico

Clinical trials that evaluate experimental treatment for patients with epilepsy often produce large placebo effects, but a recent database analysis suggests that what appears like a placebo effect may in fact result from the natural variability in patients’ response to treatment.

• Researchers conducted clinical trial simulations using data from sources including a large patient-managed seizure tracking diary database called SeizureTracker.com, a clinical trial that looked at transcranial magnetic stimulation, and a seizure diary dataset called NeuroVista, which tracks longitudinal intracranial monitoring.
• The analysis measured 50% responder rates and median percentage change.
• The clinical trial simulations were performed in 2 directions; it measured outcomes with time running forward and in reverse, ie, moving backwards from baseline through titration, to treatment.
• The analysis found that temporal reversal didn’t prevent large 50% responder rates, suggesting that what appears to be a placebo effect in clinical trials is in fact normal variability in the way patients respond to active treatment.

A multi-dataset time-reversal approach to clinical trial placebo response and the relationship to natural variability in epilepsy. Seizure. 2017; 53:31-36. DOI: http://dx.doi.org/10.1016/j.seizure.2017.10.016.

Clinical trials that evaluate experimental treatment for patients with epilepsy often produce large placebo effects, but a recent database analysis suggests that what appears like a placebo effect may in fact result from the natural variability in patients’ response to treatment.

• Researchers conducted clinical trial simulations using data from sources including a large patient-managed seizure tracking diary database called SeizureTracker.com, a clinical trial that looked at transcranial magnetic stimulation, and a seizure diary dataset called NeuroVista, which tracks longitudinal intracranial monitoring.
• The analysis measured 50% responder rates and median percentage change.
• The clinical trial simulations were performed in 2 directions; it measured outcomes with time running forward and in reverse, ie, moving backwards from baseline through titration, to treatment.
• The analysis found that temporal reversal didn’t prevent large 50% responder rates, suggesting that what appears to be a placebo effect in clinical trials is in fact normal variability in the way patients respond to active treatment.

A multi-dataset time-reversal approach to clinical trial placebo response and the relationship to natural variability in epilepsy. Seizure. 2017; 53:31-36. DOI: http://dx.doi.org/10.1016/j.seizure.2017.10.016.

Clinical trials that evaluate experimental treatment for patients with epilepsy often produce large placebo effects, but a recent database analysis suggests that what appears like a placebo effect may in fact result from the natural variability in patients’ response to treatment.

• Researchers conducted clinical trial simulations using data from sources including a large patient-managed seizure tracking diary database called SeizureTracker.com, a clinical trial that looked at transcranial magnetic stimulation, and a seizure diary dataset called NeuroVista, which tracks longitudinal intracranial monitoring.
• The analysis measured 50% responder rates and median percentage change.
• The clinical trial simulations were performed in 2 directions; it measured outcomes with time running forward and in reverse, ie, moving backwards from baseline through titration, to treatment.
• The analysis found that temporal reversal didn’t prevent large 50% responder rates, suggesting that what appears to be a placebo effect in clinical trials is in fact normal variability in the way patients respond to active treatment.

A multi-dataset time-reversal approach to clinical trial placebo response and the relationship to natural variability in epilepsy. Seizure. 2017; 53:31-36. DOI: http://dx.doi.org/10.1016/j.seizure.2017.10.016.

There are four factors at baseline in adults with moderately active rheumatoid arthritis that predict those who are most likely to achieve remission with full-dose combo etanercept-methotrexate (ETN-MTX) induction treatment, said Josef S. Smolen, MD, of the University of Vienna, and his associates.

The original PRESERVE study found that after 604 adults with moderately active rheumatoid arthritis achieved low disease activity after 36 weeks of full-dose etanercept (50 mg once weekly) plus methotrexate, subsequent full-dose or reduced-dose (25 mg once weekly) ETN-MTX combos were better at maintaining remission than was methotrexate alone. At the time of the original study, a Disease Activity Score in 28 joints (DAS28) less than 2.6 was considered to denote remission in practice and clinical trials; now that the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition of remission has been published, a DAS28 less than 2.6 no longer indicates remission according to ACR/EULAR criteria, but rather indicates minimal disease activity, the investigators explained.

This study aimed to determine predictors of remission, the researchers said in their article published in Arthritis Research & Therapy.

Those predictors at baseline are young age; body mass index less than 30 kg/m^2; lower Health Assessment Questionnaire scores; and lower disease activity – as measured by DAS28, Simplified Disease Activity Index, and Clinical Disease Activity Index.

If the predictors are favorable and the patients have an “early, strong, and durable response to induction therapy, they are most likely to experience a sustained response after biologic tapering or withdrawal,” Dr. Smolen and his associates said.

In other words, the investigators found that, the lower the residual disease activity, the greater the chance of an enduring response.

“Our findings suggest that patients who did not achieve sustained remission in the open-label period and had higher DAS28 at week 36 were more likely to lose remission with maintenance therapy in the double-blind period. Not surprisingly, patients who achieved remission at only week 36, those who sustained remission at only weeks 28 and 36, and those who sustained remission at only weeks 20, 28, and 36, were at higher risk for loss of remission than patients who sustained remission from week 12 to week 36, indicating that depth of disease control is an important predictor of remission loss,” noted Dr. Smolen and his colleagues.

This study was sponsored by Pfizer. Dr. Smolen has received research grants and consulting fees from AbbVie, Pfizer, Roche, and other biopharmaceutical companies. Several of the investigators are employees of Pfizer and hold Pfizer stock. Another author is an employee of inVentiv Health and was contracted by Pfizer to provide statistical support.

SOURCE: Smolen JS et al. Arthritis Res Ther. doi: 10.1186/s13075-017-1484-9.

There are four factors at baseline in adults with moderately active rheumatoid arthritis that predict those who are most likely to achieve remission with full-dose combo etanercept-methotrexate (ETN-MTX) induction treatment, said Josef S. Smolen, MD, of the University of Vienna, and his associates.

The original PRESERVE study found that after 604 adults with moderately active rheumatoid arthritis achieved low disease activity after 36 weeks of full-dose etanercept (50 mg once weekly) plus methotrexate, subsequent full-dose or reduced-dose (25 mg once weekly) ETN-MTX combos were better at maintaining remission than was methotrexate alone. At the time of the original study, a Disease Activity Score in 28 joints (DAS28) less than 2.6 was considered to denote remission in practice and clinical trials; now that the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition of remission has been published, a DAS28 less than 2.6 no longer indicates remission according to ACR/EULAR criteria, but rather indicates minimal disease activity, the investigators explained.

This study aimed to determine predictors of remission, the researchers said in their article published in Arthritis Research & Therapy.

Those predictors at baseline are young age; body mass index less than 30 kg/m^2; lower Health Assessment Questionnaire scores; and lower disease activity – as measured by DAS28, Simplified Disease Activity Index, and Clinical Disease Activity Index.

If the predictors are favorable and the patients have an “early, strong, and durable response to induction therapy, they are most likely to experience a sustained response after biologic tapering or withdrawal,” Dr. Smolen and his associates said.

In other words, the investigators found that, the lower the residual disease activity, the greater the chance of an enduring response.

“Our findings suggest that patients who did not achieve sustained remission in the open-label period and had higher DAS28 at week 36 were more likely to lose remission with maintenance therapy in the double-blind period. Not surprisingly, patients who achieved remission at only week 36, those who sustained remission at only weeks 28 and 36, and those who sustained remission at only weeks 20, 28, and 36, were at higher risk for loss of remission than patients who sustained remission from week 12 to week 36, indicating that depth of disease control is an important predictor of remission loss,” noted Dr. Smolen and his colleagues.

This study was sponsored by Pfizer. Dr. Smolen has received research grants and consulting fees from AbbVie, Pfizer, Roche, and other biopharmaceutical companies. Several of the investigators are employees of Pfizer and hold Pfizer stock. Another author is an employee of inVentiv Health and was contracted by Pfizer to provide statistical support.

SOURCE: Smolen JS et al. Arthritis Res Ther. doi: 10.1186/s13075-017-1484-9.

There are four factors at baseline in adults with moderately active rheumatoid arthritis that predict those who are most likely to achieve remission with full-dose combo etanercept-methotrexate (ETN-MTX) induction treatment, said Josef S. Smolen, MD, of the University of Vienna, and his associates.

The original PRESERVE study found that after 604 adults with moderately active rheumatoid arthritis achieved low disease activity after 36 weeks of full-dose etanercept (50 mg once weekly) plus methotrexate, subsequent full-dose or reduced-dose (25 mg once weekly) ETN-MTX combos were better at maintaining remission than was methotrexate alone. At the time of the original study, a Disease Activity Score in 28 joints (DAS28) less than 2.6 was considered to denote remission in practice and clinical trials; now that the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition of remission has been published, a DAS28 less than 2.6 no longer indicates remission according to ACR/EULAR criteria, but rather indicates minimal disease activity, the investigators explained.

This study aimed to determine predictors of remission, the researchers said in their article published in Arthritis Research & Therapy.

Those predictors at baseline are young age; body mass index less than 30 kg/m^2; lower Health Assessment Questionnaire scores; and lower disease activity – as measured by DAS28, Simplified Disease Activity Index, and Clinical Disease Activity Index.

If the predictors are favorable and the patients have an “early, strong, and durable response to induction therapy, they are most likely to experience a sustained response after biologic tapering or withdrawal,” Dr. Smolen and his associates said.

In other words, the investigators found that, the lower the residual disease activity, the greater the chance of an enduring response.

“Our findings suggest that patients who did not achieve sustained remission in the open-label period and had higher DAS28 at week 36 were more likely to lose remission with maintenance therapy in the double-blind period. Not surprisingly, patients who achieved remission at only week 36, those who sustained remission at only weeks 28 and 36, and those who sustained remission at only weeks 20, 28, and 36, were at higher risk for loss of remission than patients who sustained remission from week 12 to week 36, indicating that depth of disease control is an important predictor of remission loss,” noted Dr. Smolen and his colleagues.

This study was sponsored by Pfizer. Dr. Smolen has received research grants and consulting fees from AbbVie, Pfizer, Roche, and other biopharmaceutical companies. Several of the investigators are employees of Pfizer and hold Pfizer stock. Another author is an employee of inVentiv Health and was contracted by Pfizer to provide statistical support.

SOURCE: Smolen JS et al. Arthritis Res Ther. doi: 10.1186/s13075-017-1484-9.

Ictal electroencephalography (EEG) does not appear to help determine the best approach to surgery in pediatric patients if magnetic resonance imaging (MRI) findings and other presurgical data have pinpointed the epileptogenic focus, according to retrospective analysis that included 115 children.

• Investigators looked at children with epilepsy who had surgical resection based on a lesion that was identified by MRI and corroborated by other presurgical findings.
• Ictal video EEG findings were divided into 2 groups; ictal EEG findings were labeled “positive” if the identified location of the lesion agreed with the location indicated by the MRI, or “negative” if results were discordant with the MRI findings.
• The analysis found no differences in seizure-free outcomes when negative and positive EEGs were compared.
• A positive ictal EEG was not linked with better clinical outcomes regardless of the surgical site or the pathology of the lesion.
• EEGs had limited predictive value, which prompted researchers to question whether they are worth doing if MRI findings and related presurgical data confirm the location of the epileptogenic site.

MRI supersedes ictal EEG when other presurgical data are concordant. Seizure. 2017; 53:18-22. DOI: http://dx.doi.org/10.1016/j.seizure.2017.10.013.

Ictal electroencephalography (EEG) does not appear to help determine the best approach to surgery in pediatric patients if magnetic resonance imaging (MRI) findings and other presurgical data have pinpointed the epileptogenic focus, according to retrospective analysis that included 115 children.

• Investigators looked at children with epilepsy who had surgical resection based on a lesion that was identified by MRI and corroborated by other presurgical findings.
• Ictal video EEG findings were divided into 2 groups; ictal EEG findings were labeled “positive” if the identified location of the lesion agreed with the location indicated by the MRI, or “negative” if results were discordant with the MRI findings.
• The analysis found no differences in seizure-free outcomes when negative and positive EEGs were compared.
• A positive ictal EEG was not linked with better clinical outcomes regardless of the surgical site or the pathology of the lesion.
• EEGs had limited predictive value, which prompted researchers to question whether they are worth doing if MRI findings and related presurgical data confirm the location of the epileptogenic site.

MRI supersedes ictal EEG when other presurgical data are concordant. Seizure. 2017; 53:18-22. DOI: http://dx.doi.org/10.1016/j.seizure.2017.10.013.

Ictal electroencephalography (EEG) does not appear to help determine the best approach to surgery in pediatric patients if magnetic resonance imaging (MRI) findings and other presurgical data have pinpointed the epileptogenic focus, according to retrospective analysis that included 115 children.

• Investigators looked at children with epilepsy who had surgical resection based on a lesion that was identified by MRI and corroborated by other presurgical findings.
• Ictal video EEG findings were divided into 2 groups; ictal EEG findings were labeled “positive” if the identified location of the lesion agreed with the location indicated by the MRI, or “negative” if results were discordant with the MRI findings.
• The analysis found no differences in seizure-free outcomes when negative and positive EEGs were compared.
• A positive ictal EEG was not linked with better clinical outcomes regardless of the surgical site or the pathology of the lesion.
• EEGs had limited predictive value, which prompted researchers to question whether they are worth doing if MRI findings and related presurgical data confirm the location of the epileptogenic site.

MRI supersedes ictal EEG when other presurgical data are concordant. Seizure. 2017; 53:18-22. DOI: http://dx.doi.org/10.1016/j.seizure.2017.10.013.