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Bezlotoxumab reduces CDI recurrence across antibiotic subgroups
NEW ORLEANS – The monoclonal antibody bezlotoxumab significantly reduces the risk of Clostridium difficile infection (CDI) recurrence in adults receiving standard of care antibiotic treatment, regardless of whether that treatment is with metronidazole, vancomycin, or fidaxomicin, according to an analysis of data from the MODIFY I and II trials.
The global, randomized, double-blind, placebo-controlled trials demonstrated that bezlotoxumab was safe and effective for preventing CDI recurrence, and the current prespecified analysis further showed that choice of standard of care antibiotic therapy did not affect the outcomes, Erik R. Dubberke, MD, of Washington University in St. Louis, reported at IDWeek, an annual scientific meeting on infectious diseases.
Consistent with the overall study results, clinical cure rates were similar with bezlotoxumab and placebo, regardless of the standard of care antibiotic received (80% vs. 80.3%, respectively, overall; 81% vs. 81.3% in the metronidazole group; 78.5% vs. 79.6% in the vancomycin group; and 86.7% vs. 76.9% in the fidaxomicin group), he said.
However, CDI recurrence rates were lower among those who received bezlotoxumab, compared with those who received placebo in all three standard of care subgroups, with 10%, 15%, and 12% fewer bezlotoxumab vs. placebo patients experiencing recurrence in the metronidazole, vancomycin, and fidaxomicin groups, respectively, and 12% fewer experiencing recurrence overall.
The primary endpoint of CDI recurrence was defined in the studies as a new episode of diarrhea (at least three unformed stools in 24 hours) and a positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as standard of care antibiotics given for 14 days or less and no diarrhea for 2 consecutive days after completing standard of care treatment.
Of note, the patients in the vancomycin group were older and sicker, and had more risk factors for CDI, he said, noting, for example, that 57% of vancomycin patients were aged at least 65 years and 33% were aged at least 75 years, vs. 46% and 26% for metronidazole, respectively, and 46% and 18% for fidaxomicin; 72% of vancomycin patients were inpatients, compared with 65% and 50% of metronidazole and fidaxomicin patients.
Further, 19% of vancomycin patients, vs. 13% and 14% of metronidazole and fidaxomicin patients met criteria for severe CDI.
The findings of the current analysis are important, because the incidence of CDI recurrence is about 25%, and the risk increases with each subsequent recurrence, Dr. Dubberke said, concluding that this novel, nonantibiotic approach to prevention of CDI recurrence using bezlotoxumab, which recently received Food and Drug Administration approval for this indication, is of benefit for reducing that risk, regardless of the antibiotic used as part of standard of care therapy for CDI.
Dr. Dubberke reported serving as an investigator, adviser and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.
NEW ORLEANS – The monoclonal antibody bezlotoxumab significantly reduces the risk of Clostridium difficile infection (CDI) recurrence in adults receiving standard of care antibiotic treatment, regardless of whether that treatment is with metronidazole, vancomycin, or fidaxomicin, according to an analysis of data from the MODIFY I and II trials.
The global, randomized, double-blind, placebo-controlled trials demonstrated that bezlotoxumab was safe and effective for preventing CDI recurrence, and the current prespecified analysis further showed that choice of standard of care antibiotic therapy did not affect the outcomes, Erik R. Dubberke, MD, of Washington University in St. Louis, reported at IDWeek, an annual scientific meeting on infectious diseases.
Consistent with the overall study results, clinical cure rates were similar with bezlotoxumab and placebo, regardless of the standard of care antibiotic received (80% vs. 80.3%, respectively, overall; 81% vs. 81.3% in the metronidazole group; 78.5% vs. 79.6% in the vancomycin group; and 86.7% vs. 76.9% in the fidaxomicin group), he said.
However, CDI recurrence rates were lower among those who received bezlotoxumab, compared with those who received placebo in all three standard of care subgroups, with 10%, 15%, and 12% fewer bezlotoxumab vs. placebo patients experiencing recurrence in the metronidazole, vancomycin, and fidaxomicin groups, respectively, and 12% fewer experiencing recurrence overall.
The primary endpoint of CDI recurrence was defined in the studies as a new episode of diarrhea (at least three unformed stools in 24 hours) and a positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as standard of care antibiotics given for 14 days or less and no diarrhea for 2 consecutive days after completing standard of care treatment.
Of note, the patients in the vancomycin group were older and sicker, and had more risk factors for CDI, he said, noting, for example, that 57% of vancomycin patients were aged at least 65 years and 33% were aged at least 75 years, vs. 46% and 26% for metronidazole, respectively, and 46% and 18% for fidaxomicin; 72% of vancomycin patients were inpatients, compared with 65% and 50% of metronidazole and fidaxomicin patients.
Further, 19% of vancomycin patients, vs. 13% and 14% of metronidazole and fidaxomicin patients met criteria for severe CDI.
The findings of the current analysis are important, because the incidence of CDI recurrence is about 25%, and the risk increases with each subsequent recurrence, Dr. Dubberke said, concluding that this novel, nonantibiotic approach to prevention of CDI recurrence using bezlotoxumab, which recently received Food and Drug Administration approval for this indication, is of benefit for reducing that risk, regardless of the antibiotic used as part of standard of care therapy for CDI.
Dr. Dubberke reported serving as an investigator, adviser and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.
NEW ORLEANS – The monoclonal antibody bezlotoxumab significantly reduces the risk of Clostridium difficile infection (CDI) recurrence in adults receiving standard of care antibiotic treatment, regardless of whether that treatment is with metronidazole, vancomycin, or fidaxomicin, according to an analysis of data from the MODIFY I and II trials.
The global, randomized, double-blind, placebo-controlled trials demonstrated that bezlotoxumab was safe and effective for preventing CDI recurrence, and the current prespecified analysis further showed that choice of standard of care antibiotic therapy did not affect the outcomes, Erik R. Dubberke, MD, of Washington University in St. Louis, reported at IDWeek, an annual scientific meeting on infectious diseases.
Consistent with the overall study results, clinical cure rates were similar with bezlotoxumab and placebo, regardless of the standard of care antibiotic received (80% vs. 80.3%, respectively, overall; 81% vs. 81.3% in the metronidazole group; 78.5% vs. 79.6% in the vancomycin group; and 86.7% vs. 76.9% in the fidaxomicin group), he said.
However, CDI recurrence rates were lower among those who received bezlotoxumab, compared with those who received placebo in all three standard of care subgroups, with 10%, 15%, and 12% fewer bezlotoxumab vs. placebo patients experiencing recurrence in the metronidazole, vancomycin, and fidaxomicin groups, respectively, and 12% fewer experiencing recurrence overall.
The primary endpoint of CDI recurrence was defined in the studies as a new episode of diarrhea (at least three unformed stools in 24 hours) and a positive stool test for toxigenic C. difficile after clinical cure of the baseline CDI episode. Clinical cure was defined as standard of care antibiotics given for 14 days or less and no diarrhea for 2 consecutive days after completing standard of care treatment.
Of note, the patients in the vancomycin group were older and sicker, and had more risk factors for CDI, he said, noting, for example, that 57% of vancomycin patients were aged at least 65 years and 33% were aged at least 75 years, vs. 46% and 26% for metronidazole, respectively, and 46% and 18% for fidaxomicin; 72% of vancomycin patients were inpatients, compared with 65% and 50% of metronidazole and fidaxomicin patients.
Further, 19% of vancomycin patients, vs. 13% and 14% of metronidazole and fidaxomicin patients met criteria for severe CDI.
The findings of the current analysis are important, because the incidence of CDI recurrence is about 25%, and the risk increases with each subsequent recurrence, Dr. Dubberke said, concluding that this novel, nonantibiotic approach to prevention of CDI recurrence using bezlotoxumab, which recently received Food and Drug Administration approval for this indication, is of benefit for reducing that risk, regardless of the antibiotic used as part of standard of care therapy for CDI.
Dr. Dubberke reported serving as an investigator, adviser and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.
AT IDWEEK 2016
Key clinical point:
Major finding: 12% fewer bezlotoxumab vs. placebo patients experienced CDI recurrence.
Data source: A prespecified analysis of data from 1,554 subjects from the MODIFY I and II trials.
Disclosures: Dr. Dubberke reported serving as an investigator, adviser, and/or consultant for Merck, Rebiotix, Sanofi Pasteur, and Summit, and receiving consultant fees and/or grant/research support from these companies.
Diabetes, stroke linked to recurrent C. difficile
LAS VEGAS – Diabetes and stroke are risk factors for recurrent Clostridium difficile infection (CDI), with stroke patients at about 10 times the risk of recurrence.
The underlying cause for the association is a mystery, but one-sided paralysis is one possibility. “A lot of stroke patients may be hemiplegic, and they may be bedridden, so that may be a risk factor by itself. It’s something that may need to be studied in the future,” Alan Putrus, MD, a gastroenterology fellow at St. John Providence Hospital, Detroit, said in an interview.
CDI recurrence rates range from 5% to 47%, depending on the institution. Although risk factors of initial CDI have been well defined, few studies have looked at risk factors associated with recurrence.
In order to get at the question, the researchers conducted a study of 108 initial CDIs and 113 recurrences at two urban and one suburban hospital. Patients who experienced recurrence were matched 1:1 to age- and gender-matched controls with no recurrent CDI.
CDI recurrence rates were 16.5% and 15.9% in the two urban hospitals, and 14.9% in the suburban hospital.
Logistic regression revealed risk factors associated with CDI recurrence, including diabetes (odds ratio, 1.91; 95% confidence interval, 1.05-3.47; P = .04), stroke (OR, 9.73; 95% CI, 1.15-82.35; P = .04), exposure to proton pump inhibitors in the past 3 months (OR, 1.82; 95% CI, 1.03-3.23; P = .04), and admission to an intensive care unit in the past 3 months (OR, 1.95; 95% CI, 1.0-3.83; P = .04).
The results suggest that diabetes and especially stroke may be important risk factors for CDI recurrence, and their presence should prompt physicians to alter patient care accordingly, according to Dr. Putrus.
He stressed the importance of antibiotic stewardship. “Once you find a certain bug or pathogen, try to deescalate the antibiotics as soon as you can. If a patient is diabetic, controlling their blood sugar may also help,” Dr. Putrus said.
Finally, physicians should consider whether proton pump inhibitors are really necessary. Some patients start on PPIs but remain on the drugs long after symptoms have abated. “A lot of patients just have some discomfort in their abdomen, and they never stop taking it. They keep refilling it. So that’s a problem,” said Dr. Putrus.
Dr. Putrus has declared no conflicts of interest.
AGA Resource
AGA offers information to educate your patients about C. difficile and fecal microbiota transplant. Learn more at http://www.gastro.org/patient-care/conditions-diseases/clostridium-difficile-infection.
LAS VEGAS – Diabetes and stroke are risk factors for recurrent Clostridium difficile infection (CDI), with stroke patients at about 10 times the risk of recurrence.
The underlying cause for the association is a mystery, but one-sided paralysis is one possibility. “A lot of stroke patients may be hemiplegic, and they may be bedridden, so that may be a risk factor by itself. It’s something that may need to be studied in the future,” Alan Putrus, MD, a gastroenterology fellow at St. John Providence Hospital, Detroit, said in an interview.
CDI recurrence rates range from 5% to 47%, depending on the institution. Although risk factors of initial CDI have been well defined, few studies have looked at risk factors associated with recurrence.
In order to get at the question, the researchers conducted a study of 108 initial CDIs and 113 recurrences at two urban and one suburban hospital. Patients who experienced recurrence were matched 1:1 to age- and gender-matched controls with no recurrent CDI.
CDI recurrence rates were 16.5% and 15.9% in the two urban hospitals, and 14.9% in the suburban hospital.
Logistic regression revealed risk factors associated with CDI recurrence, including diabetes (odds ratio, 1.91; 95% confidence interval, 1.05-3.47; P = .04), stroke (OR, 9.73; 95% CI, 1.15-82.35; P = .04), exposure to proton pump inhibitors in the past 3 months (OR, 1.82; 95% CI, 1.03-3.23; P = .04), and admission to an intensive care unit in the past 3 months (OR, 1.95; 95% CI, 1.0-3.83; P = .04).
The results suggest that diabetes and especially stroke may be important risk factors for CDI recurrence, and their presence should prompt physicians to alter patient care accordingly, according to Dr. Putrus.
He stressed the importance of antibiotic stewardship. “Once you find a certain bug or pathogen, try to deescalate the antibiotics as soon as you can. If a patient is diabetic, controlling their blood sugar may also help,” Dr. Putrus said.
Finally, physicians should consider whether proton pump inhibitors are really necessary. Some patients start on PPIs but remain on the drugs long after symptoms have abated. “A lot of patients just have some discomfort in their abdomen, and they never stop taking it. They keep refilling it. So that’s a problem,” said Dr. Putrus.
Dr. Putrus has declared no conflicts of interest.
AGA Resource
AGA offers information to educate your patients about C. difficile and fecal microbiota transplant. Learn more at http://www.gastro.org/patient-care/conditions-diseases/clostridium-difficile-infection.
LAS VEGAS – Diabetes and stroke are risk factors for recurrent Clostridium difficile infection (CDI), with stroke patients at about 10 times the risk of recurrence.
The underlying cause for the association is a mystery, but one-sided paralysis is one possibility. “A lot of stroke patients may be hemiplegic, and they may be bedridden, so that may be a risk factor by itself. It’s something that may need to be studied in the future,” Alan Putrus, MD, a gastroenterology fellow at St. John Providence Hospital, Detroit, said in an interview.
CDI recurrence rates range from 5% to 47%, depending on the institution. Although risk factors of initial CDI have been well defined, few studies have looked at risk factors associated with recurrence.
In order to get at the question, the researchers conducted a study of 108 initial CDIs and 113 recurrences at two urban and one suburban hospital. Patients who experienced recurrence were matched 1:1 to age- and gender-matched controls with no recurrent CDI.
CDI recurrence rates were 16.5% and 15.9% in the two urban hospitals, and 14.9% in the suburban hospital.
Logistic regression revealed risk factors associated with CDI recurrence, including diabetes (odds ratio, 1.91; 95% confidence interval, 1.05-3.47; P = .04), stroke (OR, 9.73; 95% CI, 1.15-82.35; P = .04), exposure to proton pump inhibitors in the past 3 months (OR, 1.82; 95% CI, 1.03-3.23; P = .04), and admission to an intensive care unit in the past 3 months (OR, 1.95; 95% CI, 1.0-3.83; P = .04).
The results suggest that diabetes and especially stroke may be important risk factors for CDI recurrence, and their presence should prompt physicians to alter patient care accordingly, according to Dr. Putrus.
He stressed the importance of antibiotic stewardship. “Once you find a certain bug or pathogen, try to deescalate the antibiotics as soon as you can. If a patient is diabetic, controlling their blood sugar may also help,” Dr. Putrus said.
Finally, physicians should consider whether proton pump inhibitors are really necessary. Some patients start on PPIs but remain on the drugs long after symptoms have abated. “A lot of patients just have some discomfort in their abdomen, and they never stop taking it. They keep refilling it. So that’s a problem,” said Dr. Putrus.
Dr. Putrus has declared no conflicts of interest.
AGA Resource
AGA offers information to educate your patients about C. difficile and fecal microbiota transplant. Learn more at http://www.gastro.org/patient-care/conditions-diseases/clostridium-difficile-infection.
AT ACG 2016
Key clinical point:
Major finding: Diabetes, stroke, and a history of PPI use were all associated with higher risks of recurrence.
Data source: Case-control, retrospective study.
Disclosures: Dr. Putrus has declared no conflicts of interest.
Ozanimod has lasting effect on ulcerative colitis
LAS VEGAS – Ozanimod, an oral agent that selectively modulates the sphingosine 1-phosphate (S1P) 1 and 5 receptor, has a lasting effect on symptoms of ulcerative colitis, according to results from an open-label extension study.
The study extends the phase II TOUCHSTONE trial, in which patients with ulcerative colitis showed significant clinical improvement out to 32 weeks. The current study showed those improvements lasting out to at least 1 year, with about 80% of patients staying on the drug at the end of the study.
With other drug regimens, “the loss rates are at least 50% of the patients, so this is a remarkable level of durability over time,” William Sandborn, MD, chief of gastroenterology at the University of California at San Diego, said at the annual meeting of the American College of Gastroenterology. “With biologics, if you follow patients out for a year or 2, you see a fair amount of loss of response and some of that probably has to do with the formation of antidrug antibodies and immunogenicity,” Dr. Sandborn added.
In the original TOUCHSTONE study, 197 patients were randomized to placebo, ozanimod 0.5 mg, or ozanimod 1.0 mg, and followed out to week 32. Twenty-one percent of those in the 1.0-mg group achieved clinical remission, compared with 26% in the 0.5-mg group and 6% of those receiving placebo. Clinical response rates were 51%, 35%, and 20%, respectively.
In the open-label study, patients from all arms who did not respond to treatment after the induction phase, or relapsed during the maintenance phase, or completed the maintenance phase (170 patients in total) entered the open-label study with a dose of 1.0 mg ozanimod. At the time of the cut-off, patients in the extension study had been taking ozanimod for at least 1 year.
At the start of the extension study, the partial Mayo Score (pMS) for patients on placebo, ozanimod 0.5 mg, and 1.0 mg were 4.6, 4.5, and 3.3, respectively. All groups showed improvement in pMS by week 44 (1.7, 1.7, and 1.9, respectively)
At week 44, 90.9% of patients had little or no active disease (physician global assessment 0 or 1), 98.4% had little or no blood in their stools, and 84.7% had no blood in their stools.
Adverse events with a frequency higher than 2% included ulcerative colitis flare (5.9%), anemia (3.5%), upper respiratory tract infection (4.1%), nasal pharyngitis (3.5%), back pain (2.9%), arthralgia (2.4%), and headache (2.4%). The researchers noted some transient elevation of alanine aminotransferase or aspartate aminotransferase, but these elevations were temporary and reversed during ongoing treatment; 2.4% of patients experienced ALT and AST levels higher than three times the upper limit of normal, and all were asymptomatic.
Serious adverse events that occurred in two or more patients included anemia (1.2%) and ulcerative colitis flare (2.4%).
“This is a promising oral product with a similar mechanism of action to other lymphocyte trafficking agents,” said Stephen Hanauer, MD, medical director of the digestive health center at the Northwestern University, Chicago, who attended the session.
Ozanimod and other lymphocyte trafficking agents may offer a slightly different profile than some of the other drug classes, such as the anti–tumor necrosis factor agents, according to Dr. Hanauer, because the agents don’t affect lymphocytes already in the tissues. On the other hand, once the drug has acted, its effect may linger. “The time to effect may be a little slower, but the long-term effect seems to be as good or better as other mechanisms of action.”
The drug’s real place could be in early disease, Dr. Hanauer said. “If this is truly an effective and safe agent, the real positioning should be earlier in the disease, before patients are exposed to steroids and other immune suppressants, or biologics that have an infection risk.”
Celgene funded the study. Dr. Sandborn has received funding from Receptos and Celgene and consulted for both companies. Dr. Hanauer has consulted with Receptos, Celgene, Pfizer, Jansen, and AbbVie.
AGA Resource
AGA offers an IBD Clinical Service Line that provides tools to help you become more efficient, understand quality standards, and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/ibd
LAS VEGAS – Ozanimod, an oral agent that selectively modulates the sphingosine 1-phosphate (S1P) 1 and 5 receptor, has a lasting effect on symptoms of ulcerative colitis, according to results from an open-label extension study.
The study extends the phase II TOUCHSTONE trial, in which patients with ulcerative colitis showed significant clinical improvement out to 32 weeks. The current study showed those improvements lasting out to at least 1 year, with about 80% of patients staying on the drug at the end of the study.
With other drug regimens, “the loss rates are at least 50% of the patients, so this is a remarkable level of durability over time,” William Sandborn, MD, chief of gastroenterology at the University of California at San Diego, said at the annual meeting of the American College of Gastroenterology. “With biologics, if you follow patients out for a year or 2, you see a fair amount of loss of response and some of that probably has to do with the formation of antidrug antibodies and immunogenicity,” Dr. Sandborn added.
In the original TOUCHSTONE study, 197 patients were randomized to placebo, ozanimod 0.5 mg, or ozanimod 1.0 mg, and followed out to week 32. Twenty-one percent of those in the 1.0-mg group achieved clinical remission, compared with 26% in the 0.5-mg group and 6% of those receiving placebo. Clinical response rates were 51%, 35%, and 20%, respectively.
In the open-label study, patients from all arms who did not respond to treatment after the induction phase, or relapsed during the maintenance phase, or completed the maintenance phase (170 patients in total) entered the open-label study with a dose of 1.0 mg ozanimod. At the time of the cut-off, patients in the extension study had been taking ozanimod for at least 1 year.
At the start of the extension study, the partial Mayo Score (pMS) for patients on placebo, ozanimod 0.5 mg, and 1.0 mg were 4.6, 4.5, and 3.3, respectively. All groups showed improvement in pMS by week 44 (1.7, 1.7, and 1.9, respectively)
At week 44, 90.9% of patients had little or no active disease (physician global assessment 0 or 1), 98.4% had little or no blood in their stools, and 84.7% had no blood in their stools.
Adverse events with a frequency higher than 2% included ulcerative colitis flare (5.9%), anemia (3.5%), upper respiratory tract infection (4.1%), nasal pharyngitis (3.5%), back pain (2.9%), arthralgia (2.4%), and headache (2.4%). The researchers noted some transient elevation of alanine aminotransferase or aspartate aminotransferase, but these elevations were temporary and reversed during ongoing treatment; 2.4% of patients experienced ALT and AST levels higher than three times the upper limit of normal, and all were asymptomatic.
Serious adverse events that occurred in two or more patients included anemia (1.2%) and ulcerative colitis flare (2.4%).
“This is a promising oral product with a similar mechanism of action to other lymphocyte trafficking agents,” said Stephen Hanauer, MD, medical director of the digestive health center at the Northwestern University, Chicago, who attended the session.
Ozanimod and other lymphocyte trafficking agents may offer a slightly different profile than some of the other drug classes, such as the anti–tumor necrosis factor agents, according to Dr. Hanauer, because the agents don’t affect lymphocytes already in the tissues. On the other hand, once the drug has acted, its effect may linger. “The time to effect may be a little slower, but the long-term effect seems to be as good or better as other mechanisms of action.”
The drug’s real place could be in early disease, Dr. Hanauer said. “If this is truly an effective and safe agent, the real positioning should be earlier in the disease, before patients are exposed to steroids and other immune suppressants, or biologics that have an infection risk.”
Celgene funded the study. Dr. Sandborn has received funding from Receptos and Celgene and consulted for both companies. Dr. Hanauer has consulted with Receptos, Celgene, Pfizer, Jansen, and AbbVie.
AGA Resource
AGA offers an IBD Clinical Service Line that provides tools to help you become more efficient, understand quality standards, and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/ibd
LAS VEGAS – Ozanimod, an oral agent that selectively modulates the sphingosine 1-phosphate (S1P) 1 and 5 receptor, has a lasting effect on symptoms of ulcerative colitis, according to results from an open-label extension study.
The study extends the phase II TOUCHSTONE trial, in which patients with ulcerative colitis showed significant clinical improvement out to 32 weeks. The current study showed those improvements lasting out to at least 1 year, with about 80% of patients staying on the drug at the end of the study.
With other drug regimens, “the loss rates are at least 50% of the patients, so this is a remarkable level of durability over time,” William Sandborn, MD, chief of gastroenterology at the University of California at San Diego, said at the annual meeting of the American College of Gastroenterology. “With biologics, if you follow patients out for a year or 2, you see a fair amount of loss of response and some of that probably has to do with the formation of antidrug antibodies and immunogenicity,” Dr. Sandborn added.
In the original TOUCHSTONE study, 197 patients were randomized to placebo, ozanimod 0.5 mg, or ozanimod 1.0 mg, and followed out to week 32. Twenty-one percent of those in the 1.0-mg group achieved clinical remission, compared with 26% in the 0.5-mg group and 6% of those receiving placebo. Clinical response rates were 51%, 35%, and 20%, respectively.
In the open-label study, patients from all arms who did not respond to treatment after the induction phase, or relapsed during the maintenance phase, or completed the maintenance phase (170 patients in total) entered the open-label study with a dose of 1.0 mg ozanimod. At the time of the cut-off, patients in the extension study had been taking ozanimod for at least 1 year.
At the start of the extension study, the partial Mayo Score (pMS) for patients on placebo, ozanimod 0.5 mg, and 1.0 mg were 4.6, 4.5, and 3.3, respectively. All groups showed improvement in pMS by week 44 (1.7, 1.7, and 1.9, respectively)
At week 44, 90.9% of patients had little or no active disease (physician global assessment 0 or 1), 98.4% had little or no blood in their stools, and 84.7% had no blood in their stools.
Adverse events with a frequency higher than 2% included ulcerative colitis flare (5.9%), anemia (3.5%), upper respiratory tract infection (4.1%), nasal pharyngitis (3.5%), back pain (2.9%), arthralgia (2.4%), and headache (2.4%). The researchers noted some transient elevation of alanine aminotransferase or aspartate aminotransferase, but these elevations were temporary and reversed during ongoing treatment; 2.4% of patients experienced ALT and AST levels higher than three times the upper limit of normal, and all were asymptomatic.
Serious adverse events that occurred in two or more patients included anemia (1.2%) and ulcerative colitis flare (2.4%).
“This is a promising oral product with a similar mechanism of action to other lymphocyte trafficking agents,” said Stephen Hanauer, MD, medical director of the digestive health center at the Northwestern University, Chicago, who attended the session.
Ozanimod and other lymphocyte trafficking agents may offer a slightly different profile than some of the other drug classes, such as the anti–tumor necrosis factor agents, according to Dr. Hanauer, because the agents don’t affect lymphocytes already in the tissues. On the other hand, once the drug has acted, its effect may linger. “The time to effect may be a little slower, but the long-term effect seems to be as good or better as other mechanisms of action.”
The drug’s real place could be in early disease, Dr. Hanauer said. “If this is truly an effective and safe agent, the real positioning should be earlier in the disease, before patients are exposed to steroids and other immune suppressants, or biologics that have an infection risk.”
Celgene funded the study. Dr. Sandborn has received funding from Receptos and Celgene and consulted for both companies. Dr. Hanauer has consulted with Receptos, Celgene, Pfizer, Jansen, and AbbVie.
AGA Resource
AGA offers an IBD Clinical Service Line that provides tools to help you become more efficient, understand quality standards, and improve the process of care for patients. Learn more at http://www.gastro.org/patient-care/conditions-diseases/ibd
AT ACG 2016
Key clinical point:
Major finding: Ozanimod maintains efficacy in ulcerative colitis out to 1 year, with 90% of patients having little or no evidence of active disease.
Data source: Open-label extension study following a phase II clinical trial.
Disclosures: Celgene funded the study. Dr. Sandborn has received funding from Receptos and Celgene and consulted for both companies. Dr. Hanauer has consulted with Receptos, Celgene, Pfizer, Jansen, and AbbVie.
ACR 2016 continues big buffet of basic and clinical science sessions
This year’s annual meeting of the American College of Rheumatology will feature cutting-edge research and results of studies that directly affect how attendees will manage patients once they are back in the clinical setting, according to both Richard Loeser, MD, program chair of the Annual Meeting Planning Committee (AMPC), and Gregory Gardner, MD, clinical subchair of the AMPC, who suggested special sessions of interest culled from the more than 450 sessions to be presented.
“It is an exciting time in rheumatology. Basic research is being translated into new therapies before our very eyes. Areas on the program this year that have translational potential include immunometabolism, blocking interleukin-1 (IL-1), T-cell receptor signaling, and meta-analysis of gene expression data. The meeting will also feature trials that refine and advance the management of rheumatologic diseases, including results on studies of new biologics,” Dr. Loeser said.
Hot sessions
Luke O’Neill, MD, will talk about immunometabolism Monday at 7:30 a.m. This session will explore a newly described connection between energy metabolism and the immune system and the link with inflammation.
Charles Dinarello, MD, will give the Philip Hensch Memorial Lecture Sunday at 8:30 a.m. on blocking IL-1 in inflammatory diseases. He will cover a host of diseases from gout to cancer, Dr. Loeser noted.
Another hot topic, T-cell receptor signaling in autoimmune diseases and the development of new therapies, will be discussed by Arthur Weiss, MD, Tuesday morning at 7:30 a.m.
Tuesday at 11:00 a.m., Peter Lipsky, MD, will tackle big data mining, presenting a meta-analysis of gene expression datasets to identify novel pathways and targets in systemic lupus erythematosus (SLE).
“SLE lags behind rheumatoid arthritis in therapeutic advances. A number of trials of biologics have failed in SLE, whereas they have been found effective in rheumatoid arthritis,” Dr. Loeser explained.
Clinical slant
Sunday’s Plenary session at 11:00 a.m. will feature several top-rated abstracts, among them results of a phase III study on tocilizumab in giant cell arteritis to be presented by John Stone, MD. “Tocilizumab is a major breakthrough as a steroid-sparing treatment for the most common form of vasculitis that affects older adults,” Dr. Loeser said.
At 2:30 p.m. on Sunday at The Great Debate, Paul Emery, MD, and Arthur Kavanaugh, MD, will tackle the very important clinical topic of “To Taper or Not to Taper? – Biologic DMARDs in Low Rheumatoid Arthritis Disease Activity.”
“People aren’t sure what to do. The fear with tapering is rebound, with the disease coming back even more forcefully. There is new evidence to suggest that tapering may be safe under certain circumstances. This session should inform attendees on how to make the decision to taper and on the best way to do it,” Dr. Loeser commented.
The Late-Breaking Abstract session on Tuesday at 4:30 p.m. will feature six clinical trials. Dr. Loeser singled out a study to be presented by Elaine Husni, MD, on “Vascular Safety of Celecoxib versus Ibuprofen or Naproxen” in more than 20,000 patients with osteoarthritis or rheumatoid arthritis.
“The fear is that COX-2 inhibitors have increased cardiovascular risk. The data from this study that will be presented at the meeting should answer the question of whether or not this is true in patients with arthritis,” Dr. Loeser explained.
Wednesday at 7:30 a.m. Candida Fratazzi, MD, will talk about “Emerging Biosimilars in Therapeutic Management,” a subject of great interest since they have the potential to be equally effective and less expensive than current biologics.
Two “bookends” of the meeting will frame the opening and closing. Sunday at 7:30 a.m., the “Year in Review” session will feature the best published studies on rheumatologic diseases from the past year, based on the judgment of two experts. Ingrid Lundberg, MD, will present the best clinical studies and Bruce Cronstein, MD, will present the best basic science studies. Wednesday at 7:30 a.m., John Cush, MD, and Dr. Kavanaugh will present the “Rheumatology Roundup” of the best abstracts and put them into context. “This session is usually quite entertaining,” Dr. Loeser said.
More sessions of clinical import
“In keeping with our meeting theme of fine-tuning our care of patients with rheumatic disease, I want to point out several sessions,” Dr. Gardner said.
Attendees interested in sessions on clinical applicability will have to choose between two different sessions Monday at 4:30 p.m.: one on dermatomyositis, a relatively rare but difficult-to-treat entity, and the other about treatment of the patient with rheumatoid arthritis when the patient is not well and suffering from comorbidities.
Monday at 8:30 a.m., an “Osteoporosis Update” will give listeners perspective on current and future therapies.
Sunday at 2:30 p.m., new guidelines for steroid-induced osteoporosis will be presented.
“Four or five sessions on the Tech Track will show rheumatologists how they can improve their practice by using technology,” Dr. Gardner said. “Several high-quality sessions are important to educators, including ‘Flipped Classroom, Technology, and Reflection’ [Monday at 12:30 p.m.] and ‘Year in Review’ [Sunday at 1:00 p.m.].”
Monday at 11:00 a.m., the Plenary session will feature Workforce Study results on how many rheumatologists will be needed in the year 2030, and in which geographic locations. This session will also include a discussion of the impact of part-time rheumatologists.
“Two sessions I am excited about are ‘Treat to Target in 2016,’ Tuesday at 4:30 p.m., and ‘Rheumatic Diseases in Native Americans,’ Sunday at 11:00 a.m.,” Dr. Gardner noted. “Concurrent abstract sessions throughout the meeting will feature discussions on new biologics, small molecules, and gene therapy.”
This year’s annual meeting of the American College of Rheumatology will feature cutting-edge research and results of studies that directly affect how attendees will manage patients once they are back in the clinical setting, according to both Richard Loeser, MD, program chair of the Annual Meeting Planning Committee (AMPC), and Gregory Gardner, MD, clinical subchair of the AMPC, who suggested special sessions of interest culled from the more than 450 sessions to be presented.
“It is an exciting time in rheumatology. Basic research is being translated into new therapies before our very eyes. Areas on the program this year that have translational potential include immunometabolism, blocking interleukin-1 (IL-1), T-cell receptor signaling, and meta-analysis of gene expression data. The meeting will also feature trials that refine and advance the management of rheumatologic diseases, including results on studies of new biologics,” Dr. Loeser said.
Hot sessions
Luke O’Neill, MD, will talk about immunometabolism Monday at 7:30 a.m. This session will explore a newly described connection between energy metabolism and the immune system and the link with inflammation.
Charles Dinarello, MD, will give the Philip Hensch Memorial Lecture Sunday at 8:30 a.m. on blocking IL-1 in inflammatory diseases. He will cover a host of diseases from gout to cancer, Dr. Loeser noted.
Another hot topic, T-cell receptor signaling in autoimmune diseases and the development of new therapies, will be discussed by Arthur Weiss, MD, Tuesday morning at 7:30 a.m.
Tuesday at 11:00 a.m., Peter Lipsky, MD, will tackle big data mining, presenting a meta-analysis of gene expression datasets to identify novel pathways and targets in systemic lupus erythematosus (SLE).
“SLE lags behind rheumatoid arthritis in therapeutic advances. A number of trials of biologics have failed in SLE, whereas they have been found effective in rheumatoid arthritis,” Dr. Loeser explained.
Clinical slant
Sunday’s Plenary session at 11:00 a.m. will feature several top-rated abstracts, among them results of a phase III study on tocilizumab in giant cell arteritis to be presented by John Stone, MD. “Tocilizumab is a major breakthrough as a steroid-sparing treatment for the most common form of vasculitis that affects older adults,” Dr. Loeser said.
At 2:30 p.m. on Sunday at The Great Debate, Paul Emery, MD, and Arthur Kavanaugh, MD, will tackle the very important clinical topic of “To Taper or Not to Taper? – Biologic DMARDs in Low Rheumatoid Arthritis Disease Activity.”
“People aren’t sure what to do. The fear with tapering is rebound, with the disease coming back even more forcefully. There is new evidence to suggest that tapering may be safe under certain circumstances. This session should inform attendees on how to make the decision to taper and on the best way to do it,” Dr. Loeser commented.
The Late-Breaking Abstract session on Tuesday at 4:30 p.m. will feature six clinical trials. Dr. Loeser singled out a study to be presented by Elaine Husni, MD, on “Vascular Safety of Celecoxib versus Ibuprofen or Naproxen” in more than 20,000 patients with osteoarthritis or rheumatoid arthritis.
“The fear is that COX-2 inhibitors have increased cardiovascular risk. The data from this study that will be presented at the meeting should answer the question of whether or not this is true in patients with arthritis,” Dr. Loeser explained.
Wednesday at 7:30 a.m. Candida Fratazzi, MD, will talk about “Emerging Biosimilars in Therapeutic Management,” a subject of great interest since they have the potential to be equally effective and less expensive than current biologics.
Two “bookends” of the meeting will frame the opening and closing. Sunday at 7:30 a.m., the “Year in Review” session will feature the best published studies on rheumatologic diseases from the past year, based on the judgment of two experts. Ingrid Lundberg, MD, will present the best clinical studies and Bruce Cronstein, MD, will present the best basic science studies. Wednesday at 7:30 a.m., John Cush, MD, and Dr. Kavanaugh will present the “Rheumatology Roundup” of the best abstracts and put them into context. “This session is usually quite entertaining,” Dr. Loeser said.
More sessions of clinical import
“In keeping with our meeting theme of fine-tuning our care of patients with rheumatic disease, I want to point out several sessions,” Dr. Gardner said.
Attendees interested in sessions on clinical applicability will have to choose between two different sessions Monday at 4:30 p.m.: one on dermatomyositis, a relatively rare but difficult-to-treat entity, and the other about treatment of the patient with rheumatoid arthritis when the patient is not well and suffering from comorbidities.
Monday at 8:30 a.m., an “Osteoporosis Update” will give listeners perspective on current and future therapies.
Sunday at 2:30 p.m., new guidelines for steroid-induced osteoporosis will be presented.
“Four or five sessions on the Tech Track will show rheumatologists how they can improve their practice by using technology,” Dr. Gardner said. “Several high-quality sessions are important to educators, including ‘Flipped Classroom, Technology, and Reflection’ [Monday at 12:30 p.m.] and ‘Year in Review’ [Sunday at 1:00 p.m.].”
Monday at 11:00 a.m., the Plenary session will feature Workforce Study results on how many rheumatologists will be needed in the year 2030, and in which geographic locations. This session will also include a discussion of the impact of part-time rheumatologists.
“Two sessions I am excited about are ‘Treat to Target in 2016,’ Tuesday at 4:30 p.m., and ‘Rheumatic Diseases in Native Americans,’ Sunday at 11:00 a.m.,” Dr. Gardner noted. “Concurrent abstract sessions throughout the meeting will feature discussions on new biologics, small molecules, and gene therapy.”
This year’s annual meeting of the American College of Rheumatology will feature cutting-edge research and results of studies that directly affect how attendees will manage patients once they are back in the clinical setting, according to both Richard Loeser, MD, program chair of the Annual Meeting Planning Committee (AMPC), and Gregory Gardner, MD, clinical subchair of the AMPC, who suggested special sessions of interest culled from the more than 450 sessions to be presented.
“It is an exciting time in rheumatology. Basic research is being translated into new therapies before our very eyes. Areas on the program this year that have translational potential include immunometabolism, blocking interleukin-1 (IL-1), T-cell receptor signaling, and meta-analysis of gene expression data. The meeting will also feature trials that refine and advance the management of rheumatologic diseases, including results on studies of new biologics,” Dr. Loeser said.
Hot sessions
Luke O’Neill, MD, will talk about immunometabolism Monday at 7:30 a.m. This session will explore a newly described connection between energy metabolism and the immune system and the link with inflammation.
Charles Dinarello, MD, will give the Philip Hensch Memorial Lecture Sunday at 8:30 a.m. on blocking IL-1 in inflammatory diseases. He will cover a host of diseases from gout to cancer, Dr. Loeser noted.
Another hot topic, T-cell receptor signaling in autoimmune diseases and the development of new therapies, will be discussed by Arthur Weiss, MD, Tuesday morning at 7:30 a.m.
Tuesday at 11:00 a.m., Peter Lipsky, MD, will tackle big data mining, presenting a meta-analysis of gene expression datasets to identify novel pathways and targets in systemic lupus erythematosus (SLE).
“SLE lags behind rheumatoid arthritis in therapeutic advances. A number of trials of biologics have failed in SLE, whereas they have been found effective in rheumatoid arthritis,” Dr. Loeser explained.
Clinical slant
Sunday’s Plenary session at 11:00 a.m. will feature several top-rated abstracts, among them results of a phase III study on tocilizumab in giant cell arteritis to be presented by John Stone, MD. “Tocilizumab is a major breakthrough as a steroid-sparing treatment for the most common form of vasculitis that affects older adults,” Dr. Loeser said.
At 2:30 p.m. on Sunday at The Great Debate, Paul Emery, MD, and Arthur Kavanaugh, MD, will tackle the very important clinical topic of “To Taper or Not to Taper? – Biologic DMARDs in Low Rheumatoid Arthritis Disease Activity.”
“People aren’t sure what to do. The fear with tapering is rebound, with the disease coming back even more forcefully. There is new evidence to suggest that tapering may be safe under certain circumstances. This session should inform attendees on how to make the decision to taper and on the best way to do it,” Dr. Loeser commented.
The Late-Breaking Abstract session on Tuesday at 4:30 p.m. will feature six clinical trials. Dr. Loeser singled out a study to be presented by Elaine Husni, MD, on “Vascular Safety of Celecoxib versus Ibuprofen or Naproxen” in more than 20,000 patients with osteoarthritis or rheumatoid arthritis.
“The fear is that COX-2 inhibitors have increased cardiovascular risk. The data from this study that will be presented at the meeting should answer the question of whether or not this is true in patients with arthritis,” Dr. Loeser explained.
Wednesday at 7:30 a.m. Candida Fratazzi, MD, will talk about “Emerging Biosimilars in Therapeutic Management,” a subject of great interest since they have the potential to be equally effective and less expensive than current biologics.
Two “bookends” of the meeting will frame the opening and closing. Sunday at 7:30 a.m., the “Year in Review” session will feature the best published studies on rheumatologic diseases from the past year, based on the judgment of two experts. Ingrid Lundberg, MD, will present the best clinical studies and Bruce Cronstein, MD, will present the best basic science studies. Wednesday at 7:30 a.m., John Cush, MD, and Dr. Kavanaugh will present the “Rheumatology Roundup” of the best abstracts and put them into context. “This session is usually quite entertaining,” Dr. Loeser said.
More sessions of clinical import
“In keeping with our meeting theme of fine-tuning our care of patients with rheumatic disease, I want to point out several sessions,” Dr. Gardner said.
Attendees interested in sessions on clinical applicability will have to choose between two different sessions Monday at 4:30 p.m.: one on dermatomyositis, a relatively rare but difficult-to-treat entity, and the other about treatment of the patient with rheumatoid arthritis when the patient is not well and suffering from comorbidities.
Monday at 8:30 a.m., an “Osteoporosis Update” will give listeners perspective on current and future therapies.
Sunday at 2:30 p.m., new guidelines for steroid-induced osteoporosis will be presented.
“Four or five sessions on the Tech Track will show rheumatologists how they can improve their practice by using technology,” Dr. Gardner said. “Several high-quality sessions are important to educators, including ‘Flipped Classroom, Technology, and Reflection’ [Monday at 12:30 p.m.] and ‘Year in Review’ [Sunday at 1:00 p.m.].”
Monday at 11:00 a.m., the Plenary session will feature Workforce Study results on how many rheumatologists will be needed in the year 2030, and in which geographic locations. This session will also include a discussion of the impact of part-time rheumatologists.
“Two sessions I am excited about are ‘Treat to Target in 2016,’ Tuesday at 4:30 p.m., and ‘Rheumatic Diseases in Native Americans,’ Sunday at 11:00 a.m.,” Dr. Gardner noted. “Concurrent abstract sessions throughout the meeting will feature discussions on new biologics, small molecules, and gene therapy.”
FROM THE ACR ANNUAL MEETING
Study finds no increase in microcephaly with Tdap vaccine in pregnancy
The combined tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is not associated with an increased risk of microcephaly and other structural birth defects when administered during pregnancy, according to findings from a large, retrospective cohort study.
The U.S. Advisory Committee on Immunization Practices currently recommends administration of the Tdap vaccine between 27 and 36 weeks’ gestation in every pregnancy. However, the overlap of the start of Brazil’s maternal Tdap immunization in November 2014 with the substantial increase in microcephaly cases in 2015 prompted concerns of an association between the vaccine and structural birth defects.
They found that Tdap immunization was not significantly associated with an increased risk for microcephaly during any week of pregnancy (adjusted prevalence ratio, 0.86; 95% CI, 0.60-1.24). They also saw no increased risk of microcephaly when vaccinations occurred before 14 weeks’ gestation (adjusted prevalence ratio, 0.96; 95% CI, 0.36-2.58), or when vaccinations were administered between 27 weeks’ and 36 weeks’ gestation (adjusted prevalence ratio, 1.01; 95% CI, 0.63-1.61). The findings were similar for other structural defects, including congenital heart defects, spina bifida, encephalocele, and anophthalmia (JAMA. 2016;316[17]:1823-5).
“These results expand upon what is known about maternal Tdap vaccination safety to include information about structural birth defects and microcephaly in offspring,” the investigators wrote. “The findings support recommendations for routine Tdap administration during pregnancy.”
However, they noted that the study findings may have been limited by incomplete data on women’s immunization status, birth defects, and defects that may have resulted in pregnancy loss or elective termination.
The study was funded by the Centers for Disease Control and Prevention. The investigators reported having no relevant financial disclosures.
The combined tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is not associated with an increased risk of microcephaly and other structural birth defects when administered during pregnancy, according to findings from a large, retrospective cohort study.
The U.S. Advisory Committee on Immunization Practices currently recommends administration of the Tdap vaccine between 27 and 36 weeks’ gestation in every pregnancy. However, the overlap of the start of Brazil’s maternal Tdap immunization in November 2014 with the substantial increase in microcephaly cases in 2015 prompted concerns of an association between the vaccine and structural birth defects.
They found that Tdap immunization was not significantly associated with an increased risk for microcephaly during any week of pregnancy (adjusted prevalence ratio, 0.86; 95% CI, 0.60-1.24). They also saw no increased risk of microcephaly when vaccinations occurred before 14 weeks’ gestation (adjusted prevalence ratio, 0.96; 95% CI, 0.36-2.58), or when vaccinations were administered between 27 weeks’ and 36 weeks’ gestation (adjusted prevalence ratio, 1.01; 95% CI, 0.63-1.61). The findings were similar for other structural defects, including congenital heart defects, spina bifida, encephalocele, and anophthalmia (JAMA. 2016;316[17]:1823-5).
“These results expand upon what is known about maternal Tdap vaccination safety to include information about structural birth defects and microcephaly in offspring,” the investigators wrote. “The findings support recommendations for routine Tdap administration during pregnancy.”
However, they noted that the study findings may have been limited by incomplete data on women’s immunization status, birth defects, and defects that may have resulted in pregnancy loss or elective termination.
The study was funded by the Centers for Disease Control and Prevention. The investigators reported having no relevant financial disclosures.
The combined tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is not associated with an increased risk of microcephaly and other structural birth defects when administered during pregnancy, according to findings from a large, retrospective cohort study.
The U.S. Advisory Committee on Immunization Practices currently recommends administration of the Tdap vaccine between 27 and 36 weeks’ gestation in every pregnancy. However, the overlap of the start of Brazil’s maternal Tdap immunization in November 2014 with the substantial increase in microcephaly cases in 2015 prompted concerns of an association between the vaccine and structural birth defects.
They found that Tdap immunization was not significantly associated with an increased risk for microcephaly during any week of pregnancy (adjusted prevalence ratio, 0.86; 95% CI, 0.60-1.24). They also saw no increased risk of microcephaly when vaccinations occurred before 14 weeks’ gestation (adjusted prevalence ratio, 0.96; 95% CI, 0.36-2.58), or when vaccinations were administered between 27 weeks’ and 36 weeks’ gestation (adjusted prevalence ratio, 1.01; 95% CI, 0.63-1.61). The findings were similar for other structural defects, including congenital heart defects, spina bifida, encephalocele, and anophthalmia (JAMA. 2016;316[17]:1823-5).
“These results expand upon what is known about maternal Tdap vaccination safety to include information about structural birth defects and microcephaly in offspring,” the investigators wrote. “The findings support recommendations for routine Tdap administration during pregnancy.”
However, they noted that the study findings may have been limited by incomplete data on women’s immunization status, birth defects, and defects that may have resulted in pregnancy loss or elective termination.
The study was funded by the Centers for Disease Control and Prevention. The investigators reported having no relevant financial disclosures.
FROM JAMA
Key clinical point:
Major finding: Tdap immunization was not significantly associated with an increased risk for microcephaly during any week of pregnancy (adjusted prevalence ratio, 0.86; 95% CI, 0.60-1.24).
Data source: A retrospective cohort study in 41,654 singleton infants born to women who received Tdap during pregnancy and a control group of 282,809 babies born to unvaccinated women.
Disclosures: The study was funded by the Centers for Disease Control and Prevention. The investigators reported having no relevant financial disclosures.
Large increase seen in number of Zika-infected pregnancies
The 288 new cases of pregnant women in the United States with laboratory evidence of Zika infection reported for the week ending Oct. 27, 2016, represent the largest weekly increase so far this year, according to new data from the Centers for Disease Control and Prevention.
The 52 new cases in the 50 states and the District of Columbia and the 236 cases in the U.S. territories bring the totals for the year to 1,005 and 2,263, respectively, and to 3,268 for the United States as a whole, the CDC reported.
The week ending Oct. 27 also brought reports of two more infants born with Zika-related birth defects in the 50 states/D.C., but there were no reports of Zika-related pregnancy losses. So far in 2016, there have been 25 liveborn infants with Zika-related birth defects and five pregnancy losses in the states.
The CDC is no longer reporting adverse pregnancy outcomes for the territories because Puerto Rico is not using the same “inclusion criteria to monitor brain abnormalities and other adverse pregnancy outcomes.” As of Sept. 29 – the date of the last territorial report – there had been one liveborn infant and one pregnancy loss related to Zika.
Zika-related birth defects reported by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.
The pregnancy-related figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.
The 288 new cases of pregnant women in the United States with laboratory evidence of Zika infection reported for the week ending Oct. 27, 2016, represent the largest weekly increase so far this year, according to new data from the Centers for Disease Control and Prevention.
The 52 new cases in the 50 states and the District of Columbia and the 236 cases in the U.S. territories bring the totals for the year to 1,005 and 2,263, respectively, and to 3,268 for the United States as a whole, the CDC reported.
The week ending Oct. 27 also brought reports of two more infants born with Zika-related birth defects in the 50 states/D.C., but there were no reports of Zika-related pregnancy losses. So far in 2016, there have been 25 liveborn infants with Zika-related birth defects and five pregnancy losses in the states.
The CDC is no longer reporting adverse pregnancy outcomes for the territories because Puerto Rico is not using the same “inclusion criteria to monitor brain abnormalities and other adverse pregnancy outcomes.” As of Sept. 29 – the date of the last territorial report – there had been one liveborn infant and one pregnancy loss related to Zika.
Zika-related birth defects reported by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.
The pregnancy-related figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.
The 288 new cases of pregnant women in the United States with laboratory evidence of Zika infection reported for the week ending Oct. 27, 2016, represent the largest weekly increase so far this year, according to new data from the Centers for Disease Control and Prevention.
The 52 new cases in the 50 states and the District of Columbia and the 236 cases in the U.S. territories bring the totals for the year to 1,005 and 2,263, respectively, and to 3,268 for the United States as a whole, the CDC reported.
The week ending Oct. 27 also brought reports of two more infants born with Zika-related birth defects in the 50 states/D.C., but there were no reports of Zika-related pregnancy losses. So far in 2016, there have been 25 liveborn infants with Zika-related birth defects and five pregnancy losses in the states.
The CDC is no longer reporting adverse pregnancy outcomes for the territories because Puerto Rico is not using the same “inclusion criteria to monitor brain abnormalities and other adverse pregnancy outcomes.” As of Sept. 29 – the date of the last territorial report – there had been one liveborn infant and one pregnancy loss related to Zika.
Zika-related birth defects reported by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.
The pregnancy-related figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.
Treating Lower Arterial Occlusive Disease
How to proceed when a patient needs a bypass that can’t be done using the saphenous vein, and how to measure arterial flow to the foot are two novel areas that help improve a revascularization algorithm for lower arterial occlusive disease, according to Dr. Kenneth Ouriel, co-moderator of the Wednesday session, “Value of Deep Vein Grafts; New Concepts in Assessing Foot Perfusion and Improving It; More About the Angiosome Controversy; Some Ongoing CLI Trials.”
“A lot of patients don’t have a suitable bypass conduit to bring blood to the lower limb. But when the saphenous vein isn’t available, and you’re concerned an artificial graft won’t be as effective, there is another alternative,” said Dr. Ouriel, president and CEO of the New York–based clinical research firm, Syntactx.
Dr. Ouriel said “it’s also a vein that is not that long, so if you need a long vein for a bypass, from the top of the leg to the ankle, for example, it might not be long enough.”
Clinicians who attend this session also will be able to incorporate novel ways of quantifying perfusion to the foot, according to Dr. Ouriel. “The angiosome isn’t controversial so much as just new. Most of us didn’t learn about it in medical school, but we will explore it in depth during this session.”
The general principle of the angiosome is that arterial flow to the foot is “compartmentalized” into regions supplied by discrete vessels. This leads to seeing perfusion not only as a whole, but also in terms of specific regions, said Dr. Ouriel.
By focusing on the revascularization of the source artery to a specific angiosome, data indicate there are better rates of wound healing and limb salvage, according to Dr. Ouriel.
To round out the session are results and questions posed by a series of “exciting” trials both completed and still recruiting, including the LIBERTY, SPINACH, and BEST trials. The discussion of these trial findings will add nuance to the overall discussion about whether surgical reconstruction or peripheral intervention in patients with critical limb ischemia is appropriate and when to do it.
Session 30:
Value of Deep Vein Grafts; New Concepts in Assessing Foot Perfusion and Improving It; More About the Angiosome Controversy; Some Ongoing CLI Trials
Wednesday, 4:22 p.m. – 5:58 p.m.
Grand Ballroom East, 3rd Floor
How to proceed when a patient needs a bypass that can’t be done using the saphenous vein, and how to measure arterial flow to the foot are two novel areas that help improve a revascularization algorithm for lower arterial occlusive disease, according to Dr. Kenneth Ouriel, co-moderator of the Wednesday session, “Value of Deep Vein Grafts; New Concepts in Assessing Foot Perfusion and Improving It; More About the Angiosome Controversy; Some Ongoing CLI Trials.”
“A lot of patients don’t have a suitable bypass conduit to bring blood to the lower limb. But when the saphenous vein isn’t available, and you’re concerned an artificial graft won’t be as effective, there is another alternative,” said Dr. Ouriel, president and CEO of the New York–based clinical research firm, Syntactx.
Dr. Ouriel said “it’s also a vein that is not that long, so if you need a long vein for a bypass, from the top of the leg to the ankle, for example, it might not be long enough.”
Clinicians who attend this session also will be able to incorporate novel ways of quantifying perfusion to the foot, according to Dr. Ouriel. “The angiosome isn’t controversial so much as just new. Most of us didn’t learn about it in medical school, but we will explore it in depth during this session.”
The general principle of the angiosome is that arterial flow to the foot is “compartmentalized” into regions supplied by discrete vessels. This leads to seeing perfusion not only as a whole, but also in terms of specific regions, said Dr. Ouriel.
By focusing on the revascularization of the source artery to a specific angiosome, data indicate there are better rates of wound healing and limb salvage, according to Dr. Ouriel.
To round out the session are results and questions posed by a series of “exciting” trials both completed and still recruiting, including the LIBERTY, SPINACH, and BEST trials. The discussion of these trial findings will add nuance to the overall discussion about whether surgical reconstruction or peripheral intervention in patients with critical limb ischemia is appropriate and when to do it.
Session 30:
Value of Deep Vein Grafts; New Concepts in Assessing Foot Perfusion and Improving It; More About the Angiosome Controversy; Some Ongoing CLI Trials
Wednesday, 4:22 p.m. – 5:58 p.m.
Grand Ballroom East, 3rd Floor
How to proceed when a patient needs a bypass that can’t be done using the saphenous vein, and how to measure arterial flow to the foot are two novel areas that help improve a revascularization algorithm for lower arterial occlusive disease, according to Dr. Kenneth Ouriel, co-moderator of the Wednesday session, “Value of Deep Vein Grafts; New Concepts in Assessing Foot Perfusion and Improving It; More About the Angiosome Controversy; Some Ongoing CLI Trials.”
“A lot of patients don’t have a suitable bypass conduit to bring blood to the lower limb. But when the saphenous vein isn’t available, and you’re concerned an artificial graft won’t be as effective, there is another alternative,” said Dr. Ouriel, president and CEO of the New York–based clinical research firm, Syntactx.
Dr. Ouriel said “it’s also a vein that is not that long, so if you need a long vein for a bypass, from the top of the leg to the ankle, for example, it might not be long enough.”
Clinicians who attend this session also will be able to incorporate novel ways of quantifying perfusion to the foot, according to Dr. Ouriel. “The angiosome isn’t controversial so much as just new. Most of us didn’t learn about it in medical school, but we will explore it in depth during this session.”
The general principle of the angiosome is that arterial flow to the foot is “compartmentalized” into regions supplied by discrete vessels. This leads to seeing perfusion not only as a whole, but also in terms of specific regions, said Dr. Ouriel.
By focusing on the revascularization of the source artery to a specific angiosome, data indicate there are better rates of wound healing and limb salvage, according to Dr. Ouriel.
To round out the session are results and questions posed by a series of “exciting” trials both completed and still recruiting, including the LIBERTY, SPINACH, and BEST trials. The discussion of these trial findings will add nuance to the overall discussion about whether surgical reconstruction or peripheral intervention in patients with critical limb ischemia is appropriate and when to do it.
Session 30:
Value of Deep Vein Grafts; New Concepts in Assessing Foot Perfusion and Improving It; More About the Angiosome Controversy; Some Ongoing CLI Trials
Wednesday, 4:22 p.m. – 5:58 p.m.
Grand Ballroom East, 3rd Floor
U.S. preterm birth rate rose slightly in 2015
The preterm birth rate in the United States for 2015 increased for the first time in 8 years, according to the March of Dimes.
The national preterm birth rate rose from 9.57% in 2014 to 9.63% last year, earning an overall grade of C on the March of Dimes 2016 Premature Birth Report Card.
The March of Dimes also ranked preterm births in the states by racial/ethnic disparity: Maine had the least disparity, followed by New Hampshire and Utah, while Hawaii had the greatest disparity, just ahead of Pennsylvania and Louisiana. Using an average of the 2012-2014 national preterm birth rates, the March of Dimes calculated that Asian/Pacific Islanders had the lowest preterm birth rate at 8.5%, compared with 9% for whites, 9.1% for Hispanics, 10.4% for American Indian/Alaska Natives, and 13.3% for blacks.
The report card shows “that there is an unfair burden of premature birth among specific racial and ethnic groups as well as geographic areas,” Jennifer L. Howse, PhD, president of the March of Dimes, said in a statement. “Babies in this country have different chances of surviving and thriving simply based on the circumstances of their birth.”
The preterm birth rate in the United States for 2015 increased for the first time in 8 years, according to the March of Dimes.
The national preterm birth rate rose from 9.57% in 2014 to 9.63% last year, earning an overall grade of C on the March of Dimes 2016 Premature Birth Report Card.
The March of Dimes also ranked preterm births in the states by racial/ethnic disparity: Maine had the least disparity, followed by New Hampshire and Utah, while Hawaii had the greatest disparity, just ahead of Pennsylvania and Louisiana. Using an average of the 2012-2014 national preterm birth rates, the March of Dimes calculated that Asian/Pacific Islanders had the lowest preterm birth rate at 8.5%, compared with 9% for whites, 9.1% for Hispanics, 10.4% for American Indian/Alaska Natives, and 13.3% for blacks.
The report card shows “that there is an unfair burden of premature birth among specific racial and ethnic groups as well as geographic areas,” Jennifer L. Howse, PhD, president of the March of Dimes, said in a statement. “Babies in this country have different chances of surviving and thriving simply based on the circumstances of their birth.”
The preterm birth rate in the United States for 2015 increased for the first time in 8 years, according to the March of Dimes.
The national preterm birth rate rose from 9.57% in 2014 to 9.63% last year, earning an overall grade of C on the March of Dimes 2016 Premature Birth Report Card.
The March of Dimes also ranked preterm births in the states by racial/ethnic disparity: Maine had the least disparity, followed by New Hampshire and Utah, while Hawaii had the greatest disparity, just ahead of Pennsylvania and Louisiana. Using an average of the 2012-2014 national preterm birth rates, the March of Dimes calculated that Asian/Pacific Islanders had the lowest preterm birth rate at 8.5%, compared with 9% for whites, 9.1% for Hispanics, 10.4% for American Indian/Alaska Natives, and 13.3% for blacks.
The report card shows “that there is an unfair burden of premature birth among specific racial and ethnic groups as well as geographic areas,” Jennifer L. Howse, PhD, president of the March of Dimes, said in a statement. “Babies in this country have different chances of surviving and thriving simply based on the circumstances of their birth.”
Switching Between Generic AEDs Not Linked to Hospital Visits for Seizure
Switching between generic versions of the same antiepileptic drug made by different manufacturers does not appear to change the risk of seizure-related events in patients with epilepsy, according to a population-based, case–crossover study of generic antiepileptic drug users published online ahead of print September 28 in Neurology. Delays and complications of the medication refilling process might increase a patient’s risk for a seizure, said Aaron Kesselheim, MD, JD, MPH, Associate Professor of Medicine at Harvard Medical School in Boston, and colleagues. 
“These results add to the growing literature supporting the routine use of interchangeable generic [antiepileptic drugs] among patients with seizure disorders,” he added.
Although previous observational studies have demonstrated increased seizure activity following a switch from brand name to generic antiepileptic drugs, several recent randomized trials have found no
link between generic drug switching and seizure risk, said Dr. Kesselheim.
Investigators identified 59,344 patients with at least one refill of a prescription from the same manufacturer and 5,200 patients who switched from one generic to another from 2000 to 2010 in the Medicaid Analytic eXtract database and from 2005 to 2013 in a commercial health insurance database. Participants acted as their own controls in the study’s comparison of the effects of a refill or a refill with a switch in manufacturer on seizure-related events (ie, a seizure requiring an emergency department visit or hospitalization) during a hazard period, defined as days 2–36 preceding a seizure-related event, and a control period, defined as days 51–85 preceding the seizure-related event.
Overall, generic antiepileptic refilling of the same medication from the same manufacturer was associated with an 8% increase in the odds of having a seizure-related event. When the refill involved a switch to the same generic drug made by a different manufacturer, the odds of a seizure-related event rose by 9%. When the refill involved a change in the shape or color of the pill, the odds increased by 11% but did not increase when the switch was made to a pill with the same color and shape. The increased odds of seizure-related events became nonsignificant when the researchers adjusted these comparisons for the process of refilling, which “is often not straightforward,” said Dr. Kesselheim. “Patients have expressed frustration with delays and other complicating factors relating to refilling.… Greater work to enhance the refilling process, and to determine whether mail order pharmacies successfully improve outcomes on this point, is necessary.”
The study was not supported by any specific targeted funding. The investigators received support from various foundations and from programs within Harvard University and grants from the Agency for Healthcare Research and Quality and the FDA.The investigators also disclosed acting in a research support role for or receiving financial compensation from several pharmaceutical companies and other organizations.
—Jessica Craig
Suggested Reading
Kesselheim AS, Bykov K, Gagne JJ, et al. Switching generic antiepileptic drug manufacturer not linked to seizures: a case-crossover study. Neurology. 2016 Sep 28 [Epub ahead of print].
Krauss GL, Privitera M. More data on the safety of generic substitution: yes, the blue tablet is OK? Neurology. 2016 Sep 28 [Epub ahead of print].
Switching between generic versions of the same antiepileptic drug made by different manufacturers does not appear to change the risk of seizure-related events in patients with epilepsy, according to a population-based, case–crossover study of generic antiepileptic drug users published online ahead of print September 28 in Neurology. Delays and complications of the medication refilling process might increase a patient’s risk for a seizure, said Aaron Kesselheim, MD, JD, MPH, Associate Professor of Medicine at Harvard Medical School in Boston, and colleagues.
“These results add to the growing literature supporting the routine use of interchangeable generic [antiepileptic drugs] among patients with seizure disorders,” he added.
Although previous observational studies have demonstrated increased seizure activity following a switch from brand name to generic antiepileptic drugs, several recent randomized trials have found no
link between generic drug switching and seizure risk, said Dr. Kesselheim.
Investigators identified 59,344 patients with at least one refill of a prescription from the same manufacturer and 5,200 patients who switched from one generic to another from 2000 to 2010 in the Medicaid Analytic eXtract database and from 2005 to 2013 in a commercial health insurance database. Participants acted as their own controls in the study’s comparison of the effects of a refill or a refill with a switch in manufacturer on seizure-related events (ie, a seizure requiring an emergency department visit or hospitalization) during a hazard period, defined as days 2–36 preceding a seizure-related event, and a control period, defined as days 51–85 preceding the seizure-related event.
Overall, generic antiepileptic refilling of the same medication from the same manufacturer was associated with an 8% increase in the odds of having a seizure-related event. When the refill involved a switch to the same generic drug made by a different manufacturer, the odds of a seizure-related event rose by 9%. When the refill involved a change in the shape or color of the pill, the odds increased by 11% but did not increase when the switch was made to a pill with the same color and shape. The increased odds of seizure-related events became nonsignificant when the researchers adjusted these comparisons for the process of refilling, which “is often not straightforward,” said Dr. Kesselheim. “Patients have expressed frustration with delays and other complicating factors relating to refilling.… Greater work to enhance the refilling process, and to determine whether mail order pharmacies successfully improve outcomes on this point, is necessary.”
The study was not supported by any specific targeted funding. The investigators received support from various foundations and from programs within Harvard University and grants from the Agency for Healthcare Research and Quality and the FDA.The investigators also disclosed acting in a research support role for or receiving financial compensation from several pharmaceutical companies and other organizations.
—Jessica Craig
Suggested Reading
Kesselheim AS, Bykov K, Gagne JJ, et al. Switching generic antiepileptic drug manufacturer not linked to seizures: a case-crossover study. Neurology. 2016 Sep 28 [Epub ahead of print].
Krauss GL, Privitera M. More data on the safety of generic substitution: yes, the blue tablet is OK? Neurology. 2016 Sep 28 [Epub ahead of print].
Switching between generic versions of the same antiepileptic drug made by different manufacturers does not appear to change the risk of seizure-related events in patients with epilepsy, according to a population-based, case–crossover study of generic antiepileptic drug users published online ahead of print September 28 in Neurology. Delays and complications of the medication refilling process might increase a patient’s risk for a seizure, said Aaron Kesselheim, MD, JD, MPH, Associate Professor of Medicine at Harvard Medical School in Boston, and colleagues.
“These results add to the growing literature supporting the routine use of interchangeable generic [antiepileptic drugs] among patients with seizure disorders,” he added.
Although previous observational studies have demonstrated increased seizure activity following a switch from brand name to generic antiepileptic drugs, several recent randomized trials have found no
link between generic drug switching and seizure risk, said Dr. Kesselheim.
Investigators identified 59,344 patients with at least one refill of a prescription from the same manufacturer and 5,200 patients who switched from one generic to another from 2000 to 2010 in the Medicaid Analytic eXtract database and from 2005 to 2013 in a commercial health insurance database. Participants acted as their own controls in the study’s comparison of the effects of a refill or a refill with a switch in manufacturer on seizure-related events (ie, a seizure requiring an emergency department visit or hospitalization) during a hazard period, defined as days 2–36 preceding a seizure-related event, and a control period, defined as days 51–85 preceding the seizure-related event.
Overall, generic antiepileptic refilling of the same medication from the same manufacturer was associated with an 8% increase in the odds of having a seizure-related event. When the refill involved a switch to the same generic drug made by a different manufacturer, the odds of a seizure-related event rose by 9%. When the refill involved a change in the shape or color of the pill, the odds increased by 11% but did not increase when the switch was made to a pill with the same color and shape. The increased odds of seizure-related events became nonsignificant when the researchers adjusted these comparisons for the process of refilling, which “is often not straightforward,” said Dr. Kesselheim. “Patients have expressed frustration with delays and other complicating factors relating to refilling.… Greater work to enhance the refilling process, and to determine whether mail order pharmacies successfully improve outcomes on this point, is necessary.”
The study was not supported by any specific targeted funding. The investigators received support from various foundations and from programs within Harvard University and grants from the Agency for Healthcare Research and Quality and the FDA.The investigators also disclosed acting in a research support role for or receiving financial compensation from several pharmaceutical companies and other organizations.
—Jessica Craig
Suggested Reading
Kesselheim AS, Bykov K, Gagne JJ, et al. Switching generic antiepileptic drug manufacturer not linked to seizures: a case-crossover study. Neurology. 2016 Sep 28 [Epub ahead of print].
Krauss GL, Privitera M. More data on the safety of generic substitution: yes, the blue tablet is OK? Neurology. 2016 Sep 28 [Epub ahead of print].
COMMENTARY—Study Reaffirms FDA Findings
The study by Dr. Kesselheim and his colleagues is one of several recently aimed at reviewing the overall safety of generic drug switching. The FDA sponsored three clinical bioequivalence studies to determine the adequacy of average bioequivalence studies for ensuring safe conversion between different antiseizure products for patients with epilepsy. Taken together, these studies confirm that most patients can safely switch between generic formulations, even between tablets differing in appearance.
So why do patients and open series report seizures associated with formulation changes? Probably several things are happening:
• Patients want to find a reason for the near-random pattern of their seizures. Threshold cortical epileptogenic activity triggers seizures in near-random patterns, and their timing might be influenced by triggers such as missing doses, stress, and hormonal changes.
• Patients’ views of illness and treatments might influence their reporting of seizures and drug effects. This search for seizure explanations can even extend to pets with seizures.
• There is temporal variability in individual drug absorption and elimination. Food has a major effect on absorption of antiseizure medications and maximum concentration; this effect is particularly common with modified-release formulations. A small subgroup of patients in the FDA’s clinical bioequivalence studies had variability in concentrations during reexposure to the same product.
• A small group of patients may be outside the 90% confidence interval bioequivalence acceptance range and may experience product switching effects.
—Gregory L. Krauss, MD
Professor of Neurology
Johns Hopkins University, Baltimore
—Michael D. Privitera, MD
Professor of Neurology
University of Cincinnati
This commentary was adapted from Krauss GL, Privitera M. More data on the safety of generic substitution: yes, the blue tablet is OK? Neurology. 2016 Sep 28 [Epub ahead of print].
The study by Dr. Kesselheim and his colleagues is one of several recently aimed at reviewing the overall safety of generic drug switching. The FDA sponsored three clinical bioequivalence studies to determine the adequacy of average bioequivalence studies for ensuring safe conversion between different antiseizure products for patients with epilepsy. Taken together, these studies confirm that most patients can safely switch between generic formulations, even between tablets differing in appearance.
So why do patients and open series report seizures associated with formulation changes? Probably several things are happening:
• Patients want to find a reason for the near-random pattern of their seizures. Threshold cortical epileptogenic activity triggers seizures in near-random patterns, and their timing might be influenced by triggers such as missing doses, stress, and hormonal changes.
• Patients’ views of illness and treatments might influence their reporting of seizures and drug effects. This search for seizure explanations can even extend to pets with seizures.
• There is temporal variability in individual drug absorption and elimination. Food has a major effect on absorption of antiseizure medications and maximum concentration; this effect is particularly common with modified-release formulations. A small subgroup of patients in the FDA’s clinical bioequivalence studies had variability in concentrations during reexposure to the same product.
• A small group of patients may be outside the 90% confidence interval bioequivalence acceptance range and may experience product switching effects.
—Gregory L. Krauss, MD
Professor of Neurology
Johns Hopkins University, Baltimore
—Michael D. Privitera, MD
Professor of Neurology
University of Cincinnati
This commentary was adapted from Krauss GL, Privitera M. More data on the safety of generic substitution: yes, the blue tablet is OK? Neurology. 2016 Sep 28 [Epub ahead of print].
The study by Dr. Kesselheim and his colleagues is one of several recently aimed at reviewing the overall safety of generic drug switching. The FDA sponsored three clinical bioequivalence studies to determine the adequacy of average bioequivalence studies for ensuring safe conversion between different antiseizure products for patients with epilepsy. Taken together, these studies confirm that most patients can safely switch between generic formulations, even between tablets differing in appearance.
So why do patients and open series report seizures associated with formulation changes? Probably several things are happening:
• Patients want to find a reason for the near-random pattern of their seizures. Threshold cortical epileptogenic activity triggers seizures in near-random patterns, and their timing might be influenced by triggers such as missing doses, stress, and hormonal changes.
• Patients’ views of illness and treatments might influence their reporting of seizures and drug effects. This search for seizure explanations can even extend to pets with seizures.
• There is temporal variability in individual drug absorption and elimination. Food has a major effect on absorption of antiseizure medications and maximum concentration; this effect is particularly common with modified-release formulations. A small subgroup of patients in the FDA’s clinical bioequivalence studies had variability in concentrations during reexposure to the same product.
• A small group of patients may be outside the 90% confidence interval bioequivalence acceptance range and may experience product switching effects.
—Gregory L. Krauss, MD
Professor of Neurology
Johns Hopkins University, Baltimore
—Michael D. Privitera, MD
Professor of Neurology
University of Cincinnati
This commentary was adapted from Krauss GL, Privitera M. More data on the safety of generic substitution: yes, the blue tablet is OK? Neurology. 2016 Sep 28 [Epub ahead of print].