An investigational antibody-drug conjugate labeled SGN-CD70A showed signs of efficacy against relapsed or refractory non-Hodgkin lymphomas in a phase 1 trial, but its future is clouded by a high incidence of treatment-associated thrombocytopenia, investigators reported.

Among 20 patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other histologies, SGN-CD70A was associated with one complete remission (CR) and three partial remissions (PR), two of which were ongoing at nearly 43 weeks of follow-up.

However, 15 of the 20 patients (75%) had treatment-related thrombocytopenias, and 13 of these adverse events (AEs) were grade 3 or greater in severity, reported Tycel Phillips, MD, of the University of Michigan, Ann Arbor, and his colleagues.

Notwithstanding the antibody-drug conjugate’s apparent efficacy in this early trial, “the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term of response with limited drug exposure. Given that we are currently unable to mitigate this AE, the rationale for further investigation of SGN-CD70A remains limited and is, therefore, not planned,” they wrote in the journal Investigational New Drugs.

SGN-CD70A consists of an antibody directed against the plasma membrane protein CD70, a protease-cleavable linker, and a DNA-crosslinking pyrrolobenzodiazepine dimer drug. Its mechanism of action is via double-strand DNA breaks in CD70-positive cells that eventually cause programmed cell death.

Dr. Phillips and his colleagues reported on the high-risk non-Hodgkin lymphoma cohort in the phase 1 trial. The cohort included nine patients with DLBCL, five with mantle cell lymphoma, two with transformed DLBCL, one with T- cell/histocyte–rich large B cell lymphoma, and three with unspecified NHL histologies.

The patients had undergone a median of 3.5 prior lines of systemic therapy, and all had relatively good performance status, with Eastern Cooperative Oncology Group scores of 0 or 1.

Patients were started on intravenous SGN-CD70A at a dose of 8 mcg/kg on day 1 of each 3-week cycle, with a planned dose escalation to 200 mcg/kg, The protocol was amended to dosing every 6 weeks, however, after the investigators observed prolonged thrombocytopenias in some patients. A total of 12 patients were treated every 3 weeks, and 8 were treated every 6 weeks.

The most common treatment-related AEs were thrombocytopenias, which occurred in three-quarters of all patients, and were largely grade 3 or greater in severity. Other treatment-related AEs of grade 3 or greater occurring in more than one patient include neutropenia in six patients; anemia in five patients; and congestive heart failure, Clostridium difficile infections, dyspnea, and decreased forced expiratory volume in two patients each.

Other common AEs were nausea and fatigue.

The investigators noted that the cause of the deep and durable thrombocytopenias could not be determined, despite assessment of known biomarkers for this complication.

The duration of the thrombocytopenia and the fact that some of the few responses that did occur were also durable after the end of treatment suggest that the dimer drug, the cytotoxic “payload” of the antibody-drug conjugate, was responsible for the effects they observed, the authors said.

The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.

SOURCE: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.

An investigational antibody-drug conjugate labeled SGN-CD70A showed signs of efficacy against relapsed or refractory non-Hodgkin lymphomas in a phase 1 trial, but its future is clouded by a high incidence of treatment-associated thrombocytopenia, investigators reported.

Among 20 patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other histologies, SGN-CD70A was associated with one complete remission (CR) and three partial remissions (PR), two of which were ongoing at nearly 43 weeks of follow-up.

However, 15 of the 20 patients (75%) had treatment-related thrombocytopenias, and 13 of these adverse events (AEs) were grade 3 or greater in severity, reported Tycel Phillips, MD, of the University of Michigan, Ann Arbor, and his colleagues.

Notwithstanding the antibody-drug conjugate’s apparent efficacy in this early trial, “the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term of response with limited drug exposure. Given that we are currently unable to mitigate this AE, the rationale for further investigation of SGN-CD70A remains limited and is, therefore, not planned,” they wrote in the journal Investigational New Drugs.

SGN-CD70A consists of an antibody directed against the plasma membrane protein CD70, a protease-cleavable linker, and a DNA-crosslinking pyrrolobenzodiazepine dimer drug. Its mechanism of action is via double-strand DNA breaks in CD70-positive cells that eventually cause programmed cell death.

Dr. Phillips and his colleagues reported on the high-risk non-Hodgkin lymphoma cohort in the phase 1 trial. The cohort included nine patients with DLBCL, five with mantle cell lymphoma, two with transformed DLBCL, one with T- cell/histocyte–rich large B cell lymphoma, and three with unspecified NHL histologies.

The patients had undergone a median of 3.5 prior lines of systemic therapy, and all had relatively good performance status, with Eastern Cooperative Oncology Group scores of 0 or 1.

Patients were started on intravenous SGN-CD70A at a dose of 8 mcg/kg on day 1 of each 3-week cycle, with a planned dose escalation to 200 mcg/kg, The protocol was amended to dosing every 6 weeks, however, after the investigators observed prolonged thrombocytopenias in some patients. A total of 12 patients were treated every 3 weeks, and 8 were treated every 6 weeks.

The most common treatment-related AEs were thrombocytopenias, which occurred in three-quarters of all patients, and were largely grade 3 or greater in severity. Other treatment-related AEs of grade 3 or greater occurring in more than one patient include neutropenia in six patients; anemia in five patients; and congestive heart failure, Clostridium difficile infections, dyspnea, and decreased forced expiratory volume in two patients each.

Other common AEs were nausea and fatigue.

The investigators noted that the cause of the deep and durable thrombocytopenias could not be determined, despite assessment of known biomarkers for this complication.

The duration of the thrombocytopenia and the fact that some of the few responses that did occur were also durable after the end of treatment suggest that the dimer drug, the cytotoxic “payload” of the antibody-drug conjugate, was responsible for the effects they observed, the authors said.

The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.

SOURCE: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.

An investigational antibody-drug conjugate labeled SGN-CD70A showed signs of efficacy against relapsed or refractory non-Hodgkin lymphomas in a phase 1 trial, but its future is clouded by a high incidence of treatment-associated thrombocytopenia, investigators reported.

Among 20 patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, and other histologies, SGN-CD70A was associated with one complete remission (CR) and three partial remissions (PR), two of which were ongoing at nearly 43 weeks of follow-up.

However, 15 of the 20 patients (75%) had treatment-related thrombocytopenias, and 13 of these adverse events (AEs) were grade 3 or greater in severity, reported Tycel Phillips, MD, of the University of Michigan, Ann Arbor, and his colleagues.

Notwithstanding the antibody-drug conjugate’s apparent efficacy in this early trial, “the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term of response with limited drug exposure. Given that we are currently unable to mitigate this AE, the rationale for further investigation of SGN-CD70A remains limited and is, therefore, not planned,” they wrote in the journal Investigational New Drugs.

SGN-CD70A consists of an antibody directed against the plasma membrane protein CD70, a protease-cleavable linker, and a DNA-crosslinking pyrrolobenzodiazepine dimer drug. Its mechanism of action is via double-strand DNA breaks in CD70-positive cells that eventually cause programmed cell death.

Dr. Phillips and his colleagues reported on the high-risk non-Hodgkin lymphoma cohort in the phase 1 trial. The cohort included nine patients with DLBCL, five with mantle cell lymphoma, two with transformed DLBCL, one with T- cell/histocyte–rich large B cell lymphoma, and three with unspecified NHL histologies.

The patients had undergone a median of 3.5 prior lines of systemic therapy, and all had relatively good performance status, with Eastern Cooperative Oncology Group scores of 0 or 1.

Patients were started on intravenous SGN-CD70A at a dose of 8 mcg/kg on day 1 of each 3-week cycle, with a planned dose escalation to 200 mcg/kg, The protocol was amended to dosing every 6 weeks, however, after the investigators observed prolonged thrombocytopenias in some patients. A total of 12 patients were treated every 3 weeks, and 8 were treated every 6 weeks.

The most common treatment-related AEs were thrombocytopenias, which occurred in three-quarters of all patients, and were largely grade 3 or greater in severity. Other treatment-related AEs of grade 3 or greater occurring in more than one patient include neutropenia in six patients; anemia in five patients; and congestive heart failure, Clostridium difficile infections, dyspnea, and decreased forced expiratory volume in two patients each.

Other common AEs were nausea and fatigue.

The investigators noted that the cause of the deep and durable thrombocytopenias could not be determined, despite assessment of known biomarkers for this complication.

The duration of the thrombocytopenia and the fact that some of the few responses that did occur were also durable after the end of treatment suggest that the dimer drug, the cytotoxic “payload” of the antibody-drug conjugate, was responsible for the effects they observed, the authors said.

The study was funded by Seattle Genetics. Dr. Phillips reported advisory board membership with the company, and four of the coauthors are employees of the company with equity interests.

SOURCE: Phillips T et al. Invest New Drugs. 2018 Aug 22. doi: 10.1007/s10637-018-0655-0.

Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).

These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.

The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 10⁹ per liter, and 40 mg if their baseline platelet count was 40-50 x 10⁹ per liter. Procedures were scheduled for 10-13 days after treatment initiation.

“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 10⁹ platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).

Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 10⁹ per liter, and they all remained asymptomatic, the investigators said.

Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.

SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.

Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).

These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.

The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 10⁹ per liter, and 40 mg if their baseline platelet count was 40-50 x 10⁹ per liter. Procedures were scheduled for 10-13 days after treatment initiation.

“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 10⁹ platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).

Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 10⁹ per liter, and they all remained asymptomatic, the investigators said.

Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.

SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.

Once-daily treatment with the oral second-generation thrombopoietin agonist avatrombopag (Doptelet) significantly reduced the need for platelet transfusion and rescue therapy for up to 7 days after patients with chronic liver disease and thrombocytopenia underwent scheduled procedures, according to the results of two international, randomized, double-blind, phase III, placebo-controlled trials reported in the September issue of Gastroenterology.

SOURCE: AMERICAN GASTROENTEROLOGICAL ASSOCIATION

In the ADAPT-1 trial, 66% of patients in the 60-mg arm met this primary endpoint, as did 88% of patients who received 40 mg for less severe thrombocytopenia, versus 23% and 38% of the placebo arms, respectively (P less than .001 for each comparison). In the ADAPT-2 trial, 69% of the 60-mg group met the primary endpoint, as did 88% of the 40-mg group, versus 35% and 33% of the respective placebo groups (P less than .001 for each comparison).

These results led the Food and Drug Administration to approve avatrombopag in May 2018 under its priority review process. The novel therapy “may be a safe and effective alternative to platelet transfusions” that could simplify the clinical management of patients with chronic liver disease and thrombocytopenia, Norah Terrault, MD, MPH, and her associates wrote in Gastroenterology.

The ADAPT-1 study included 231 patients, while ADAPT-2 included 204 patients. In each trial, patients were randomized on a 2:1 basis to receive oral avatrombopag or placebo once daily for 5 consecutive days. Patients in the intervention arms received 60 mg avatrombopag if their baseline platelet count was less than 40 x 10⁹ per liter, and 40 mg if their baseline platelet count was 40-50 x 10⁹ per liter. Procedures were scheduled for 10-13 days after treatment initiation.

“Platelet counts increased by [treatment] day 4, peaked at days 10-13, and then returned to baseline levels by day 35,” the researchers reported. Among ADAPT-1 patients with low baseline counts, 69% of avatrombopag recipients reached a prespecified target of at least 50 x 10⁹ platelets per liter on their procedure day, versus 4% of placebo recipients (P less than .0001). Corresponding proportions in ADAPT-2 were 67% and 7%, respectively (P less than .0001). Among patients with higher baseline counts, 88% and 20% achieved the target, respectively, in ADAPT-1 (P less than .0001), as did 93% versus 39%, respectively, in ADAPT-2 (P less than .0001).

Avatrombopag and placebo produced similar rates of treatment-emergent adverse events. These most often consisted of abdominal pain, dyspepsia, nausea, pyrexia, dizziness, and headache. Only three avatrombopag patients developed platelet counts above 200 x 10⁹ per liter, and they all remained asymptomatic, the investigators said.

Dova Pharmaceuticals makes avatrombopag and funded medical writing support. Dr. Terrault and three coinvestigators disclosed ties to AbbVie, Allergan, Bristol-Myers Squibb, Eisai, Gilead, Merck, and other pharmaceutical companies. One coinvestigator is chief medical officer of Dova, helped analyze the data and write the manuscript, and gave final approval of the submitted version.

SOURCE: Terrault N et al. Gastroenterology. 2018 May 17. doi: 10.1053/j.gastro.2018.05.025.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community forum to seek advice from fellow GIs on therapy and disease management options, best practices and diagnoses.

In case you missed it, here are the most popular clinical cases shared in the forum recently:

1. Ulcerative colitis
A 24-year-old male with severe pancolitis is in remission and currently functioning well, but the attending GI is fearful that a relapse is impending based on a fecal calprotectin of 1258 in a “clinically stable patient on long term maximal therapy.”



2. Esophageal varices on Warfarin
A 64-year-old patient with Child-Turcotte-Pugh (CTP) class A cirrhosis had an upper endoscopy that showed large esophageal varices with no prior history of bleeding. View Dr. Miguel Malespin’s take on this popular case in the August issue of AGA Perspectives.



3. Does he have IBS or what?
A 37-year-old male with psoriatic arthritis and abdominal pain experiences rectal bleeding and abnormal findings during colonoscopy.



4. Chronic pancolitis
Quite a few GI experts commented on next steps for this 77-year-old pancolitis patient who has refused biologics based on cost.



5. Pouchitis
This 40-year-old patient developed diarrhea, fever, abdominal pain and other symptoms, with observed ulceration and inflammation in the pouch and proximally.

More clinical cases and discussions are at https://community.gastro.org/discussions.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community forum to seek advice from fellow GIs on therapy and disease management options, best practices and diagnoses.

In case you missed it, here are the most popular clinical cases shared in the forum recently:

1. Ulcerative colitis
A 24-year-old male with severe pancolitis is in remission and currently functioning well, but the attending GI is fearful that a relapse is impending based on a fecal calprotectin of 1258 in a “clinically stable patient on long term maximal therapy.”



2. Esophageal varices on Warfarin
A 64-year-old patient with Child-Turcotte-Pugh (CTP) class A cirrhosis had an upper endoscopy that showed large esophageal varices with no prior history of bleeding. View Dr. Miguel Malespin’s take on this popular case in the August issue of AGA Perspectives.



3. Does he have IBS or what?
A 37-year-old male with psoriatic arthritis and abdominal pain experiences rectal bleeding and abnormal findings during colonoscopy.



4. Chronic pancolitis
Quite a few GI experts commented on next steps for this 77-year-old pancolitis patient who has refused biologics based on cost.



5. Pouchitis
This 40-year-old patient developed diarrhea, fever, abdominal pain and other symptoms, with observed ulceration and inflammation in the pouch and proximally.

More clinical cases and discussions are at https://community.gastro.org/discussions.

Physicians with difficult patient scenarios regularly bring their questions to the AGA Community forum to seek advice from fellow GIs on therapy and disease management options, best practices and diagnoses.

In case you missed it, here are the most popular clinical cases shared in the forum recently:

1. Ulcerative colitis
A 24-year-old male with severe pancolitis is in remission and currently functioning well, but the attending GI is fearful that a relapse is impending based on a fecal calprotectin of 1258 in a “clinically stable patient on long term maximal therapy.”



2. Esophageal varices on Warfarin
A 64-year-old patient with Child-Turcotte-Pugh (CTP) class A cirrhosis had an upper endoscopy that showed large esophageal varices with no prior history of bleeding. View Dr. Miguel Malespin’s take on this popular case in the August issue of AGA Perspectives.



3. Does he have IBS or what?
A 37-year-old male with psoriatic arthritis and abdominal pain experiences rectal bleeding and abnormal findings during colonoscopy.



4. Chronic pancolitis
Quite a few GI experts commented on next steps for this 77-year-old pancolitis patient who has refused biologics based on cost.



5. Pouchitis
This 40-year-old patient developed diarrhea, fever, abdominal pain and other symptoms, with observed ulceration and inflammation in the pouch and proximally.

More clinical cases and discussions are at https://community.gastro.org/discussions.

Congrats to AGA Research Foundation grantee Amir Zarrinpar, MD, PhD, from UC San Diego whose new microbiome research has been published in Nature Communications. Dr. Zarrinpar — a former AGA Microbiome Junior Investigator Research Award recipient — used his AGA funding to study cyclical fluctuations in the gut microbiome and its effects on host metabolism. This new study in Nature Communications is an unexpected finding resulting from Dr. Zarrinpar’s AGA research project with his collaborator Satchin Panda, PhD, and their colleagues in the Salk Institute.

The study, Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism, finds that mice that have their microbiomes depleted with antibiotics have decreased levels of glucose in their blood and better insulin sensitivity. The research has implications for understanding the role of the microbiome in diabetes. It also could lead to better insight into the side effects seen in people who are being treated with high levels of antibiotics.

The next steps for Dr. Zarrinpar and his team are to better understand what bacterial metabolites can affect insulin sensitivity and to functionally manipulate the microbiome to alter gut signaling to treat diabetes and other metabolic diseases. We look forward to seeing additional research on this topic that can eventually translate into improvements in patient care.
 

ginews@gastro.org

Congrats to AGA Research Foundation grantee Amir Zarrinpar, MD, PhD, from UC San Diego whose new microbiome research has been published in Nature Communications. Dr. Zarrinpar — a former AGA Microbiome Junior Investigator Research Award recipient — used his AGA funding to study cyclical fluctuations in the gut microbiome and its effects on host metabolism. This new study in Nature Communications is an unexpected finding resulting from Dr. Zarrinpar’s AGA research project with his collaborator Satchin Panda, PhD, and their colleagues in the Salk Institute.

The study, Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism, finds that mice that have their microbiomes depleted with antibiotics have decreased levels of glucose in their blood and better insulin sensitivity. The research has implications for understanding the role of the microbiome in diabetes. It also could lead to better insight into the side effects seen in people who are being treated with high levels of antibiotics.

The next steps for Dr. Zarrinpar and his team are to better understand what bacterial metabolites can affect insulin sensitivity and to functionally manipulate the microbiome to alter gut signaling to treat diabetes and other metabolic diseases. We look forward to seeing additional research on this topic that can eventually translate into improvements in patient care.
 

ginews@gastro.org

Congrats to AGA Research Foundation grantee Amir Zarrinpar, MD, PhD, from UC San Diego whose new microbiome research has been published in Nature Communications. Dr. Zarrinpar — a former AGA Microbiome Junior Investigator Research Award recipient — used his AGA funding to study cyclical fluctuations in the gut microbiome and its effects on host metabolism. This new study in Nature Communications is an unexpected finding resulting from Dr. Zarrinpar’s AGA research project with his collaborator Satchin Panda, PhD, and their colleagues in the Salk Institute.

The study, Antibiotic-induced microbiome depletion alters metabolic homeostasis by affecting gut signaling and colonic metabolism, finds that mice that have their microbiomes depleted with antibiotics have decreased levels of glucose in their blood and better insulin sensitivity. The research has implications for understanding the role of the microbiome in diabetes. It also could lead to better insight into the side effects seen in people who are being treated with high levels of antibiotics.

The next steps for Dr. Zarrinpar and his team are to better understand what bacterial metabolites can affect insulin sensitivity and to functionally manipulate the microbiome to alter gut signaling to treat diabetes and other metabolic diseases. We look forward to seeing additional research on this topic that can eventually translate into improvements in patient care.
 

ginews@gastro.org

Migraine headaches occurred in 5 (3.1%) of 158 patients who underwent cerebral angiography, according to a recent observational cohort study that ascertained the frequency and type of headaches following catheter‐based cerebral angiography. Consecutive patients who underwent cerebral angiography through the transfemoral (or infrequently, radial) route were included. Each patient underwent a brief neurological assessment after the procedure and more detailed assessment was performed if any patient reported occurrence of a headache. The headaches were classified as migraine if the diagnostic criteria specified by International Headache Society were met. Headache severity was classified using a visual numeric rating scale and time to reach pain free status for 2 consecutive hours was ascertained. Researchers found:

• The median severity of migraine headaches was 10/10 and time to resolution of headaches was 120 minutes (range 60–360 minutes).
• Migraine headaches occurred in 4 (18.1%) of 22 patients with a history of migraine and 4 (23.5%) of 17 patients with regular migraine headaches (≥1 episodes per month).
• Headaches occurred in 6 (3.8%) patients who did not meet the criteria for migraine headaches.

Qureshi AI, Naseem N, Saleem MA, Potluri A, Raja F, Wallery SS. Migraine and non‐migraine headaches following diagnostic catheter‐based cerebral angiography. [Published online ahead of print August 16, 2018]. Headache. doi:10.1111/head.13377.

Migraine headaches occurred in 5 (3.1%) of 158 patients who underwent cerebral angiography, according to a recent observational cohort study that ascertained the frequency and type of headaches following catheter‐based cerebral angiography. Consecutive patients who underwent cerebral angiography through the transfemoral (or infrequently, radial) route were included. Each patient underwent a brief neurological assessment after the procedure and more detailed assessment was performed if any patient reported occurrence of a headache. The headaches were classified as migraine if the diagnostic criteria specified by International Headache Society were met. Headache severity was classified using a visual numeric rating scale and time to reach pain free status for 2 consecutive hours was ascertained. Researchers found:

• The median severity of migraine headaches was 10/10 and time to resolution of headaches was 120 minutes (range 60–360 minutes).
• Migraine headaches occurred in 4 (18.1%) of 22 patients with a history of migraine and 4 (23.5%) of 17 patients with regular migraine headaches (≥1 episodes per month).
• Headaches occurred in 6 (3.8%) patients who did not meet the criteria for migraine headaches.

Qureshi AI, Naseem N, Saleem MA, Potluri A, Raja F, Wallery SS. Migraine and non‐migraine headaches following diagnostic catheter‐based cerebral angiography. [Published online ahead of print August 16, 2018]. Headache. doi:10.1111/head.13377.

Migraine headaches occurred in 5 (3.1%) of 158 patients who underwent cerebral angiography, according to a recent observational cohort study that ascertained the frequency and type of headaches following catheter‐based cerebral angiography. Consecutive patients who underwent cerebral angiography through the transfemoral (or infrequently, radial) route were included. Each patient underwent a brief neurological assessment after the procedure and more detailed assessment was performed if any patient reported occurrence of a headache. The headaches were classified as migraine if the diagnostic criteria specified by International Headache Society were met. Headache severity was classified using a visual numeric rating scale and time to reach pain free status for 2 consecutive hours was ascertained. Researchers found:

• The median severity of migraine headaches was 10/10 and time to resolution of headaches was 120 minutes (range 60–360 minutes).
• Migraine headaches occurred in 4 (18.1%) of 22 patients with a history of migraine and 4 (23.5%) of 17 patients with regular migraine headaches (≥1 episodes per month).
• Headaches occurred in 6 (3.8%) patients who did not meet the criteria for migraine headaches.

Qureshi AI, Naseem N, Saleem MA, Potluri A, Raja F, Wallery SS. Migraine and non‐migraine headaches following diagnostic catheter‐based cerebral angiography. [Published online ahead of print August 16, 2018]. Headache. doi:10.1111/head.13377.

Children with chronic headache and migraine who are severely functionally impaired demonstrated linear improvement in pain‐specific patient‐reported outcomes over time, according to a recent study that aimed to evaluate the trajectory of recovery for children undergoing intensive interdisciplinary pain rehabilitation treatment (IIPT). A retrospective analysis was conducted of patient‐reported outcomes in a clinical database of 135 children (mean age 15.2 [SD=2.2] and 74% female) admitted to an IIPT program between the years 2008 and 2014. Available data across 5 separate time points (up to 1‐year post‐discharge) were reviewed. Researchers found:

• A statistically significant improvement was noted in pain‐specific measures of functioning, including daily functioning, emotional functioning, family functioning, and school absences over a 12‐month period.
• A more general measure of quality of life improved during the program, based upon child and parent reports, although these gains did not continue to improve post‐discharge.
• As expected, although children did not report a reduction in pain during rehabilitation, they did report a significant drop in perceived pain in the 12 months following discharge from the program.

Benore E, Webster EE, Wang L, Banez G. Longitudinal analysis of patient‐reported outcomes from an interdisciplinary pediatric pain rehabilitation program for children with chronic migraine and headache. [Published online ahead of print August 23, 2018]. Headache. doi:10.1111/head.13389.

Children with chronic headache and migraine who are severely functionally impaired demonstrated linear improvement in pain‐specific patient‐reported outcomes over time, according to a recent study that aimed to evaluate the trajectory of recovery for children undergoing intensive interdisciplinary pain rehabilitation treatment (IIPT). A retrospective analysis was conducted of patient‐reported outcomes in a clinical database of 135 children (mean age 15.2 [SD=2.2] and 74% female) admitted to an IIPT program between the years 2008 and 2014. Available data across 5 separate time points (up to 1‐year post‐discharge) were reviewed. Researchers found:

• A statistically significant improvement was noted in pain‐specific measures of functioning, including daily functioning, emotional functioning, family functioning, and school absences over a 12‐month period.
• A more general measure of quality of life improved during the program, based upon child and parent reports, although these gains did not continue to improve post‐discharge.
• As expected, although children did not report a reduction in pain during rehabilitation, they did report a significant drop in perceived pain in the 12 months following discharge from the program.

Benore E, Webster EE, Wang L, Banez G. Longitudinal analysis of patient‐reported outcomes from an interdisciplinary pediatric pain rehabilitation program for children with chronic migraine and headache. [Published online ahead of print August 23, 2018]. Headache. doi:10.1111/head.13389.

Children with chronic headache and migraine who are severely functionally impaired demonstrated linear improvement in pain‐specific patient‐reported outcomes over time, according to a recent study that aimed to evaluate the trajectory of recovery for children undergoing intensive interdisciplinary pain rehabilitation treatment (IIPT). A retrospective analysis was conducted of patient‐reported outcomes in a clinical database of 135 children (mean age 15.2 [SD=2.2] and 74% female) admitted to an IIPT program between the years 2008 and 2014. Available data across 5 separate time points (up to 1‐year post‐discharge) were reviewed. Researchers found:

• A statistically significant improvement was noted in pain‐specific measures of functioning, including daily functioning, emotional functioning, family functioning, and school absences over a 12‐month period.
• A more general measure of quality of life improved during the program, based upon child and parent reports, although these gains did not continue to improve post‐discharge.
• As expected, although children did not report a reduction in pain during rehabilitation, they did report a significant drop in perceived pain in the 12 months following discharge from the program.

Benore E, Webster EE, Wang L, Banez G. Longitudinal analysis of patient‐reported outcomes from an interdisciplinary pediatric pain rehabilitation program for children with chronic migraine and headache. [Published online ahead of print August 23, 2018]. Headache. doi:10.1111/head.13389.

Preliminary data indicate that hybrid cognitive‐behavioral therapy is feasible and acceptable for youth with co‐occurring chronic migraine and insomnia, according to a recent study. Researchers conducted a single‐arm pilot trial to evaluate the feasibility and acceptability of delivering cognitive‐behavioral therapy for insomnia to 21 youth (mean age 15.5 years) with co‐occurring chronic migraine and insomnia. Adolescents completed up to 6 individual treatment sessions over 6 to 12 weeks, and 1 booster session 1 month later. Assessments included a prospective 7‐day headache and sleep diary, and self‐report measures of insomnia, sleep quality, sleep habits, and activity limitations at pre‐treatment, immediate post‐treatment, and 3‐month follow‐up. Researchers found:

• Adolescents demonstrated good treatment adherence and families rated the intervention as highly acceptable.
• Preliminary analyses indicated improvements from pre‐treatment to post‐treatment in primary outcomes of headache days (M=4.7, SD=2.1 vs M=2.8, SD=2.7) and insomnia symptoms (M=16.9, SD=5.2 vs M=9.5, SD=6.2), which were maintained at 3‐month follow‐up (M=2.7, SD=2.8; M=9.3, SD=5.0, respectively).
• Improvements were also found in secondary outcomes of pain‐related activity limitations as well as sleep quality, sleep hygiene, and sleep patterns.

Law EF, Tham SW, Aaron RV, Dudeney J, Palermo TM. Hybrid cognitive‐behavioral therapy intervention for adolescents with co‐occurring migraine and insomnia: A single‐arm pilot trial. [Published online ahead of print August 27, 2018]. Headache. doi:10.1111/head.13355.

Preliminary data indicate that hybrid cognitive‐behavioral therapy is feasible and acceptable for youth with co‐occurring chronic migraine and insomnia, according to a recent study. Researchers conducted a single‐arm pilot trial to evaluate the feasibility and acceptability of delivering cognitive‐behavioral therapy for insomnia to 21 youth (mean age 15.5 years) with co‐occurring chronic migraine and insomnia. Adolescents completed up to 6 individual treatment sessions over 6 to 12 weeks, and 1 booster session 1 month later. Assessments included a prospective 7‐day headache and sleep diary, and self‐report measures of insomnia, sleep quality, sleep habits, and activity limitations at pre‐treatment, immediate post‐treatment, and 3‐month follow‐up. Researchers found:

• Adolescents demonstrated good treatment adherence and families rated the intervention as highly acceptable.
• Preliminary analyses indicated improvements from pre‐treatment to post‐treatment in primary outcomes of headache days (M=4.7, SD=2.1 vs M=2.8, SD=2.7) and insomnia symptoms (M=16.9, SD=5.2 vs M=9.5, SD=6.2), which were maintained at 3‐month follow‐up (M=2.7, SD=2.8; M=9.3, SD=5.0, respectively).
• Improvements were also found in secondary outcomes of pain‐related activity limitations as well as sleep quality, sleep hygiene, and sleep patterns.

Law EF, Tham SW, Aaron RV, Dudeney J, Palermo TM. Hybrid cognitive‐behavioral therapy intervention for adolescents with co‐occurring migraine and insomnia: A single‐arm pilot trial. [Published online ahead of print August 27, 2018]. Headache. doi:10.1111/head.13355.

Preliminary data indicate that hybrid cognitive‐behavioral therapy is feasible and acceptable for youth with co‐occurring chronic migraine and insomnia, according to a recent study. Researchers conducted a single‐arm pilot trial to evaluate the feasibility and acceptability of delivering cognitive‐behavioral therapy for insomnia to 21 youth (mean age 15.5 years) with co‐occurring chronic migraine and insomnia. Adolescents completed up to 6 individual treatment sessions over 6 to 12 weeks, and 1 booster session 1 month later. Assessments included a prospective 7‐day headache and sleep diary, and self‐report measures of insomnia, sleep quality, sleep habits, and activity limitations at pre‐treatment, immediate post‐treatment, and 3‐month follow‐up. Researchers found:

• Adolescents demonstrated good treatment adherence and families rated the intervention as highly acceptable.
• Preliminary analyses indicated improvements from pre‐treatment to post‐treatment in primary outcomes of headache days (M=4.7, SD=2.1 vs M=2.8, SD=2.7) and insomnia symptoms (M=16.9, SD=5.2 vs M=9.5, SD=6.2), which were maintained at 3‐month follow‐up (M=2.7, SD=2.8; M=9.3, SD=5.0, respectively).
• Improvements were also found in secondary outcomes of pain‐related activity limitations as well as sleep quality, sleep hygiene, and sleep patterns.

Law EF, Tham SW, Aaron RV, Dudeney J, Palermo TM. Hybrid cognitive‐behavioral therapy intervention for adolescents with co‐occurring migraine and insomnia: A single‐arm pilot trial. [Published online ahead of print August 27, 2018]. Headache. doi:10.1111/head.13355.

The frontal lobes are pretty important. They help us plan and concentrate, and they keep us from being impulsive and distracted. They help to override those pesky emotions that can interfere with objective thought.

In Vulcans, I imagine, the frontal lobes are huge.

We put a lot of faith into them in this field. We have to stay calm and try to reason during stressful times, often with people who aren’t quite as clear headed at that moment.

Gilitukha/Thinkstock

I think we all like to believe we’re creatures of our intellects: able to think dispassionately about the current case in front of us, to make decisions based on established facts and data. And, generally, most of us do a good job.

But sometimes it doesn’t work that way.

One day in late July, I was working my way through the usual afternoon patients at the office, checking test results, making decisions – the everyday stuff. After 20 years, this has become routine.

At 1:48, while talking to a patient, an email crossed my screen. As usual, I glanced at it to make sure it wasn’t a patient emergency ... nope. It was mine.

Because of a rapidly moving forest fire in southern California, my daughter’s summer camp was being evacuated. She was safe, but they were being moved to a high school that was being used as an evacuation center in Banning, Calif. We were asked to come get her as soon as safely possible.

And, just like that, my frontal lobes got moved to the back seat.

Granted, I didn’t panic. I didn’t cancel the patients I had waiting. I completed my current appointment, then took a few extra minutes to look at the schedule with my secretary to see where we could move the next day’s patients so I could drive to California in the morning. Then I went on with my day.

I still had three more patients left. Although none of them said anything, I’m sure they noticed I wasn’t mentally all there. I probably seemed distracted, checking my screen a few more times than I should have to see whether there were further updates. I don’t think I made any bad decisions about treatment, but I certainly wasn’t at the top of my game. A few days later, after things had settled down, I reread my notes from the day to make sure I hadn’t missed anything.

It’s a surprising reminder of how powerful the older, nonrational parts of our brains are. Although they didn’t take over, they certainly affected my ability to focus on the task at hand. There’s a reason those areas exist, too, even if we keep them hidden in our daily lives.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The frontal lobes are pretty important. They help us plan and concentrate, and they keep us from being impulsive and distracted. They help to override those pesky emotions that can interfere with objective thought.

In Vulcans, I imagine, the frontal lobes are huge.

We put a lot of faith into them in this field. We have to stay calm and try to reason during stressful times, often with people who aren’t quite as clear headed at that moment.

Gilitukha/Thinkstock

I think we all like to believe we’re creatures of our intellects: able to think dispassionately about the current case in front of us, to make decisions based on established facts and data. And, generally, most of us do a good job.

But sometimes it doesn’t work that way.

One day in late July, I was working my way through the usual afternoon patients at the office, checking test results, making decisions – the everyday stuff. After 20 years, this has become routine.

At 1:48, while talking to a patient, an email crossed my screen. As usual, I glanced at it to make sure it wasn’t a patient emergency ... nope. It was mine.

Because of a rapidly moving forest fire in southern California, my daughter’s summer camp was being evacuated. She was safe, but they were being moved to a high school that was being used as an evacuation center in Banning, Calif. We were asked to come get her as soon as safely possible.

And, just like that, my frontal lobes got moved to the back seat.

Granted, I didn’t panic. I didn’t cancel the patients I had waiting. I completed my current appointment, then took a few extra minutes to look at the schedule with my secretary to see where we could move the next day’s patients so I could drive to California in the morning. Then I went on with my day.

I still had three more patients left. Although none of them said anything, I’m sure they noticed I wasn’t mentally all there. I probably seemed distracted, checking my screen a few more times than I should have to see whether there were further updates. I don’t think I made any bad decisions about treatment, but I certainly wasn’t at the top of my game. A few days later, after things had settled down, I reread my notes from the day to make sure I hadn’t missed anything.

It’s a surprising reminder of how powerful the older, nonrational parts of our brains are. Although they didn’t take over, they certainly affected my ability to focus on the task at hand. There’s a reason those areas exist, too, even if we keep them hidden in our daily lives.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The frontal lobes are pretty important. They help us plan and concentrate, and they keep us from being impulsive and distracted. They help to override those pesky emotions that can interfere with objective thought.

In Vulcans, I imagine, the frontal lobes are huge.

We put a lot of faith into them in this field. We have to stay calm and try to reason during stressful times, often with people who aren’t quite as clear headed at that moment.

Gilitukha/Thinkstock

I think we all like to believe we’re creatures of our intellects: able to think dispassionately about the current case in front of us, to make decisions based on established facts and data. And, generally, most of us do a good job.

But sometimes it doesn’t work that way.

One day in late July, I was working my way through the usual afternoon patients at the office, checking test results, making decisions – the everyday stuff. After 20 years, this has become routine.

At 1:48, while talking to a patient, an email crossed my screen. As usual, I glanced at it to make sure it wasn’t a patient emergency ... nope. It was mine.

Because of a rapidly moving forest fire in southern California, my daughter’s summer camp was being evacuated. She was safe, but they were being moved to a high school that was being used as an evacuation center in Banning, Calif. We were asked to come get her as soon as safely possible.

And, just like that, my frontal lobes got moved to the back seat.

Granted, I didn’t panic. I didn’t cancel the patients I had waiting. I completed my current appointment, then took a few extra minutes to look at the schedule with my secretary to see where we could move the next day’s patients so I could drive to California in the morning. Then I went on with my day.

I still had three more patients left. Although none of them said anything, I’m sure they noticed I wasn’t mentally all there. I probably seemed distracted, checking my screen a few more times than I should have to see whether there were further updates. I don’t think I made any bad decisions about treatment, but I certainly wasn’t at the top of my game. A few days later, after things had settled down, I reread my notes from the day to make sure I hadn’t missed anything.

It’s a surprising reminder of how powerful the older, nonrational parts of our brains are. Although they didn’t take over, they certainly affected my ability to focus on the task at hand. There’s a reason those areas exist, too, even if we keep them hidden in our daily lives.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

In a letter to Congressional leaders, President Trump has announced a pay freeze for all civilian federal employees in 2019. The decision will not impact active duty service members who are still are expected to receive a 2.6% pay raise next year.

The decision aims to circumvent a 2.1% across the board increase and additional locality pay increases that would average 25.7%. "We must maintain efforts to put our Nation on a fiscally sustainable course, and Federal agency budgets cannot sustain such increases. Accordingly, I have determined that it is appropriate to exercise my authority to set alternative across-the-board and locality pay adjustments for 2019."

In the letter, the President disputed the notion that locality pay was important for keeping and attracting quality applicants for positions. Currently, the Veterans Health Administration has more  than 40,000 job openings.

"I have determined that for 2019, both across‑the‑board pay increases and locality pay increases will be set at zero.  These alternative pay plan decisions will not materially affect our ability to attract and retain a well‑qualified Federal workforce.

President Trump had already included the pay freeze in his budget proposal. While Congress can override the President's decision, congressional action is not expected.

In a letter to Congressional leaders, President Trump has announced a pay freeze for all civilian federal employees in 2019. The decision will not impact active duty service members who are still are expected to receive a 2.6% pay raise next year.

The decision aims to circumvent a 2.1% across the board increase and additional locality pay increases that would average 25.7%. "We must maintain efforts to put our Nation on a fiscally sustainable course, and Federal agency budgets cannot sustain such increases. Accordingly, I have determined that it is appropriate to exercise my authority to set alternative across-the-board and locality pay adjustments for 2019."

In the letter, the President disputed the notion that locality pay was important for keeping and attracting quality applicants for positions. Currently, the Veterans Health Administration has more  than 40,000 job openings.

"I have determined that for 2019, both across‑the‑board pay increases and locality pay increases will be set at zero.  These alternative pay plan decisions will not materially affect our ability to attract and retain a well‑qualified Federal workforce.

President Trump had already included the pay freeze in his budget proposal. While Congress can override the President's decision, congressional action is not expected.

In a letter to Congressional leaders, President Trump has announced a pay freeze for all civilian federal employees in 2019. The decision will not impact active duty service members who are still are expected to receive a 2.6% pay raise next year.

The decision aims to circumvent a 2.1% across the board increase and additional locality pay increases that would average 25.7%. "We must maintain efforts to put our Nation on a fiscally sustainable course, and Federal agency budgets cannot sustain such increases. Accordingly, I have determined that it is appropriate to exercise my authority to set alternative across-the-board and locality pay adjustments for 2019."

In the letter, the President disputed the notion that locality pay was important for keeping and attracting quality applicants for positions. Currently, the Veterans Health Administration has more  than 40,000 job openings.

"I have determined that for 2019, both across‑the‑board pay increases and locality pay increases will be set at zero.  These alternative pay plan decisions will not materially affect our ability to attract and retain a well‑qualified Federal workforce.

President Trump had already included the pay freeze in his budget proposal. While Congress can override the President's decision, congressional action is not expected.

The Food and Drug Administration (FDA) has approved Jivi (antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.

Jivi (formerly BAY94-9027), a DNA-derived, factor VIII concentrate, is now approved for use in previously treated adults and adolescents – aged 12 years and older – with hemophilia A.

The product is also approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.

The initial recommended prophylactic regimen is dosing twice weekly (30-40 IU/kg) with the ability to dose every 5 days (45-60 IU/kg) and to further individually adjust to less or more frequent dosing based on bleeding episodes.

The FDA’s approval of Jivi is based on results from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis (2017 Mar;15[3]:411-419). Additional results are available in the prescribing information for Jivi. The product is marketed by Bayer.

PROTECT VIII enrolled previously treated adults and adolescents with severe hemophilia A. In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, researchers evaluated Jivi for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population – 112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30-40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45-60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) for the patients who were treated twice weekly and were not eligible for randomization (n = 13) improved after their dose increase. Their median ABR decreased from 17.4 to 4.1.

The median ABR for patients who were randomized to treatment every 5 days (n = 43) was 1.9. The median ABR was also 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n = 11). The median ABR for patients who completed prophylaxis with dosing every 7 days (32/43) was 0.96. The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group.

The safety data in the prescribing information includes 221 patients from three studies. The 17 patients who received Jivi for perioperative management were excluded from the pooled safety analysis but included in the analysis for inhibitor development.

In the 148 patients aged 12 years and older who were exposed to Jivi, adverse events included abdominal pain, nausea, vomiting, injection site reactions, pyrexia, hypersensitivity, dizziness, headache, insomnia, cough, erythema, pruritus, rash, and flushing.

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult patient with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

jensmith@mdedge.com

The Food and Drug Administration (FDA) has approved Jivi (antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.

Jivi (formerly BAY94-9027), a DNA-derived, factor VIII concentrate, is now approved for use in previously treated adults and adolescents – aged 12 years and older – with hemophilia A.

The product is also approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.

The initial recommended prophylactic regimen is dosing twice weekly (30-40 IU/kg) with the ability to dose every 5 days (45-60 IU/kg) and to further individually adjust to less or more frequent dosing based on bleeding episodes.

The FDA’s approval of Jivi is based on results from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis (2017 Mar;15[3]:411-419). Additional results are available in the prescribing information for Jivi. The product is marketed by Bayer.

PROTECT VIII enrolled previously treated adults and adolescents with severe hemophilia A. In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, researchers evaluated Jivi for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population – 112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30-40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45-60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) for the patients who were treated twice weekly and were not eligible for randomization (n = 13) improved after their dose increase. Their median ABR decreased from 17.4 to 4.1.

The median ABR for patients who were randomized to treatment every 5 days (n = 43) was 1.9. The median ABR was also 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n = 11). The median ABR for patients who completed prophylaxis with dosing every 7 days (32/43) was 0.96. The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group.

The safety data in the prescribing information includes 221 patients from three studies. The 17 patients who received Jivi for perioperative management were excluded from the pooled safety analysis but included in the analysis for inhibitor development.

In the 148 patients aged 12 years and older who were exposed to Jivi, adverse events included abdominal pain, nausea, vomiting, injection site reactions, pyrexia, hypersensitivity, dizziness, headache, insomnia, cough, erythema, pruritus, rash, and flushing.

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult patient with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

jensmith@mdedge.com

The Food and Drug Administration (FDA) has approved Jivi (antihemophilic factor [recombinant] PEGylated-aucl) for the treatment of hemophilia A.

Jivi (formerly BAY94-9027), a DNA-derived, factor VIII concentrate, is now approved for use in previously treated adults and adolescents – aged 12 years and older – with hemophilia A.

The product is also approved for on-demand treatment and control of bleeding episodes, for perioperative management of bleeding, and as routine prophylaxis to reduce the frequency of bleeding episodes.

The initial recommended prophylactic regimen is dosing twice weekly (30-40 IU/kg) with the ability to dose every 5 days (45-60 IU/kg) and to further individually adjust to less or more frequent dosing based on bleeding episodes.

The FDA’s approval of Jivi is based on results from the phase 2/3 PROTECT VIII trial. Some results from this trial were published in the Journal of Thrombosis and Haemostasis (2017 Mar;15[3]:411-419). Additional results are available in the prescribing information for Jivi. The product is marketed by Bayer.

PROTECT VIII enrolled previously treated adults and adolescents with severe hemophilia A. In part A, researchers evaluated different dosing regimens for Jivi used as prophylaxis and on-demand treatment. An optional extension study was available to patients who completed part A. In part B, researchers evaluated Jivi for perioperative management.

In part A, there were 132 patients in the intent‐to‐treat population – 112 in the prophylaxis group and 20 in the on-demand group.

Patients received Jivi for 36 weeks. For the first 10 weeks, patients in the prophylaxis group received twice-weekly dosing at 25 IU/kg.

Patients with more than one bleed during this time went on to receive 30-40 IU/kg twice weekly. Patients with one or fewer bleeds were eligible for randomization to dosing every 5 days (45-60 IU/kg) or every 7 days (60 IU/kg).

The median annualized bleeding rate (ABR) for the patients who were treated twice weekly and were not eligible for randomization (n = 13) improved after their dose increase. Their median ABR decreased from 17.4 to 4.1.

The median ABR for patients who were randomized to treatment every 5 days (n = 43) was 1.9. The median ABR was also 1.9 for patients who were eligible for randomization but continued on twice-weekly treatment (n = 11). The median ABR for patients who completed prophylaxis with dosing every 7 days (32/43) was 0.96. The median ABR for patients treated on demand was 24.1.

There were 388 treated bleeds in the on-demand group and 317 treated bleeds in the prophylaxis group.

The safety data in the prescribing information includes 221 patients from three studies. The 17 patients who received Jivi for perioperative management were excluded from the pooled safety analysis but included in the analysis for inhibitor development.

In the 148 patients aged 12 years and older who were exposed to Jivi, adverse events included abdominal pain, nausea, vomiting, injection site reactions, pyrexia, hypersensitivity, dizziness, headache, insomnia, cough, erythema, pruritus, rash, and flushing.

A factor VIII inhibitor was reported in one adult patient, but repeat testing did not confirm the report.

One adult patient with asthma had a clinical hypersensitivity reaction and a transient increase of IgM anti-PEG antibody titer, which was negative upon retesting.

jensmith@mdedge.com