Video

PARK CITY, UTAH – Postpartum necrotizing fasciitis, a surgical emergency, can be set off by nothing more than a small vaginal tear or a standard cesarean incision, and it’s easy to misdiagnose at first.

There’s no pus, and the skin can look mostly normal with just a little swelling. The tipoff is pain that seems out of proportion to the clinical signs.

David Eschenbach, MD, chair of the department of obstetrics and gynecology at the University of Washington, Seattle, knows the infection well. In an interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, he shared his insights on how physicians can recognize and treat postpartum necrotizing fasciitis in time to limit the damage.

aotto@frontlinemedcom.com

PARK CITY, UTAH – Postpartum necrotizing fasciitis, a surgical emergency, can be set off by nothing more than a small vaginal tear or a standard cesarean incision, and it’s easy to misdiagnose at first.

There’s no pus, and the skin can look mostly normal with just a little swelling. The tipoff is pain that seems out of proportion to the clinical signs.

David Eschenbach, MD, chair of the department of obstetrics and gynecology at the University of Washington, Seattle, knows the infection well. In an interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, he shared his insights on how physicians can recognize and treat postpartum necrotizing fasciitis in time to limit the damage.

aotto@frontlinemedcom.com

PARK CITY, UTAH – Postpartum necrotizing fasciitis, a surgical emergency, can be set off by nothing more than a small vaginal tear or a standard cesarean incision, and it’s easy to misdiagnose at first.

There’s no pus, and the skin can look mostly normal with just a little swelling. The tipoff is pain that seems out of proportion to the clinical signs.

David Eschenbach, MD, chair of the department of obstetrics and gynecology at the University of Washington, Seattle, knows the infection well. In an interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, he shared his insights on how physicians can recognize and treat postpartum necrotizing fasciitis in time to limit the damage.

aotto@frontlinemedcom.com

PARK CITY, UTAH – Despite notable progress in recent years, there’s room to further reduce perinatal HIV infection in the United States. Early recognition and treatment of HIV infection in pregnancy, prophylaxis for at-risk women, and retention of infected women in postpartum HIV care remain important goals, but they aren’t always met.

In a wide-ranging interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, Gweneth Lazenby, MD, associate professor of obstetrics and gynecology at the Medical University of South Carolina, Charleston, explained what to do to improve the situation. Among the many pearls she shared: One HIV test isn’t enough for at-risk women.

aotto@frontlinemedcom.com

PARK CITY, UTAH – Despite notable progress in recent years, there’s room to further reduce perinatal HIV infection in the United States. Early recognition and treatment of HIV infection in pregnancy, prophylaxis for at-risk women, and retention of infected women in postpartum HIV care remain important goals, but they aren’t always met.

In a wide-ranging interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, Gweneth Lazenby, MD, associate professor of obstetrics and gynecology at the Medical University of South Carolina, Charleston, explained what to do to improve the situation. Among the many pearls she shared: One HIV test isn’t enough for at-risk women.

aotto@frontlinemedcom.com

PARK CITY, UTAH – Despite notable progress in recent years, there’s room to further reduce perinatal HIV infection in the United States. Early recognition and treatment of HIV infection in pregnancy, prophylaxis for at-risk women, and retention of infected women in postpartum HIV care remain important goals, but they aren’t always met.

In a wide-ranging interview at the annual scientific meeting of the Infectious Diseases Society for Obstetrics and Gynecology, Gweneth Lazenby, MD, associate professor of obstetrics and gynecology at the Medical University of South Carolina, Charleston, explained what to do to improve the situation. Among the many pearls she shared: One HIV test isn’t enough for at-risk women.

aotto@frontlinemedcom.com

MADRID – Catastrophic antiphospholipid syndrome (CAPS) is associated with a high mortality rate, but new research presented at the European Congress of Rheumatology shows that patient survival can be significantly improved by a triple therapy treatment approach.

Researchers at the Congress also presented clinical practice guidelines for the diagnosis and management of the rare disease, which accounts for just 1% of patients with antiphospholipid syndrome (APS).

CAPS is characterized by a fast onset of widespread thrombosis, mainly in the small vessels, and, often, microangiopathic hemolytic anemia is seen in the laboratory. If undiagnosed or left untreated, patients may present with multiorgan failure needing intensive care treatment, which can be fatal in up to 50% of cases.

At the Congress, Ignasi Rodríguez-Pintó, MD, presented new data from the CAPS Registry that looks at the combined effect of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins on the survival of patients with CAPS as well as the new clinical practice guidelines.

CAPS Registry study

The aim of the study Dr. Rodríguez-Pintó presented on behalf of the CAPS Registry Project Group was to determine what, if any, survival benefit would be incurred from a triple therapy approach when compared with other different combinations of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins, or none of these treatments.

Although the triple therapy treatment approach is already being used in practice, its use is largely empirical, Dr. Rodríguez-Pintó of the department of autoimmune disease at the Hospital Clinic, Barcelona, explained in a video interview.

The investigators derived their data from episodes of CAPS occurring in patients in the CAPS Registry from the European Forum on Antiphospholipid Antibodies. This international registry was set up in 2000 and has been assembling the clinical, laboratory, and therapeutic findings of patients with CAPS for almost 20 years.

“We observed 525 episodes of CAPS in 502 patients. That means that some patients had two to three episodes of CAPS,” Dr. Rodríguez-Pintó said. Data on 38 episodes of CAPS had to be excluded from the analysis because of missing information, which left 487 episodes occurring in 471 patients.

The mean age of the 471 patients included in the analysis was 38 years. The majority (67.9%) were female and had primary (68.8%) APS. Triple therapy was given to about 40% of patients who experienced CAPS, with about 57% receiving other combinations of drugs and 2.5% receiving no treatment for CAPS.

Overall, 177 of the 487 (36.3%) episodes of CAPS were fatal.

“Triple therapy was associated with a higher chance of survival when compared to other combinations or to none of these treatments,” Dr. Rodríguez-Pintó said.

While 28% of patients with CAPS died in the triple therapy group, mortality was 41% with other combinations of treatments and 75% with none of these treatments.

All-cause mortality was reduced by 47% with triple therapy, compared with none of these treatments. The adjusted odds ratio (aOR) when comparing survival between triple therapy and no treatment was 7.7, with a 95% confidence interval of 2.0 to 29.7. The aOR comparing other drug combinations versus none of these treatments was 6.8 (95% CI, 1.7-29.6).

“For a long time, we have been saying that triple therapy would probably be the best approach, but we had no firm evidence,” Dr. Rodríguez-Pintó said.

“So, this is the first time that we have clear clinical evidence of the benefit of these approaches, and I think that these results are important because they will give us more confidence in how we treat patients and help develop guidance on [the treatment’s] use in the future.”

Guidelines

A steering committee composed of representatives from the European Commission–funded RARE-BestPractices project and McMaster University in Hamilton, Ont., used GRADE methodology to develop the guidelines for CAPS diagnosis and management. The committee answered three diagnostic and seven treatment questions that originated from a panel of 19 international stakeholders, including Dr. Rodríguez-Pintó, through systematic reviews of the literature that used Cochrane criteria.

Although the review of studies did not include the study of CAPS Registry data that Dr. Rodríguez-Pintó and his colleagues conducted, he said that the recommendations still confirm the value of using a triple therapy approach to treatment.

The panel created three diagnostic recommendations for patients suspected of having CAPS, all of which were conditional and based on very low certainty of evidence: use preliminary CAPS classification criteria to diagnose CAPS; use or nonuse of biopsy, depending on the circumstances, because of its high specificity but possibly low sensitivity for thrombotic microangiopathy; and test for antiphospholipid antibodies, which should not delay initiation of treatment.

All seven first-line treatment recommendations that the panel developed relied on a very low certainty of evidence, and most were conditional:

• Triple therapy combination treatment with corticosteroids, heparin, and plasma exchange or intravenous immunoglobulins instead of a single agent or other combination treatments.
• Therapeutic dose anticoagulation was one of only two treatment recommendations to be considered “strong,” but use of direct oral anticoagulants is not advised.
• Therapeutic plasma exchange is recommended for use with other therapies and should be strongly considered for patients with microangiopathic hemolytic anemia.
• Intravenous immunoglobulin is advised for use in conjunction with other therapies and should be given special consideration for patients with immune thrombocytopenia or renal insufficiency.
• Antiplatelet agents are conditionally recommended as an add-on therapy, but their potential mortality benefit is tempered by increased risk of bleeding when used with anticoagulants. Strong consideration should be given to their use as an alternative therapy to anticoagulation when anticoagulation is contraindicated for a reason other than bleeding.
• Rituximab (Rituxan) should not be used because of little available data on its use, uncertainty regarding long-term consequences, and its expense – except for refractory cases where other therapies have been insufficient.
• Corticosteroids should not be used because of their lack of efficacy in CAPS when used alone and potential for adverse effects, except for certain circumstances where they may be indicated.

The authors of the guidelines emphasized that these recommendations are not meant to apply to every CAPS patient. They also noted that the available evidence did not allow for temporal analysis of treatments and that conclusions could not be drawn regarding “first-line” versus “second-line” therapies.

None of the authors of the registry study or the guidelines had relevant conflicts of interest to declare.

jevans@frontlinemedcom.com

MADRID – Catastrophic antiphospholipid syndrome (CAPS) is associated with a high mortality rate, but new research presented at the European Congress of Rheumatology shows that patient survival can be significantly improved by a triple therapy treatment approach.

Researchers at the Congress also presented clinical practice guidelines for the diagnosis and management of the rare disease, which accounts for just 1% of patients with antiphospholipid syndrome (APS).

CAPS is characterized by a fast onset of widespread thrombosis, mainly in the small vessels, and, often, microangiopathic hemolytic anemia is seen in the laboratory. If undiagnosed or left untreated, patients may present with multiorgan failure needing intensive care treatment, which can be fatal in up to 50% of cases.

At the Congress, Ignasi Rodríguez-Pintó, MD, presented new data from the CAPS Registry that looks at the combined effect of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins on the survival of patients with CAPS as well as the new clinical practice guidelines.

CAPS Registry study

The aim of the study Dr. Rodríguez-Pintó presented on behalf of the CAPS Registry Project Group was to determine what, if any, survival benefit would be incurred from a triple therapy approach when compared with other different combinations of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins, or none of these treatments.

Although the triple therapy treatment approach is already being used in practice, its use is largely empirical, Dr. Rodríguez-Pintó of the department of autoimmune disease at the Hospital Clinic, Barcelona, explained in a video interview.

The investigators derived their data from episodes of CAPS occurring in patients in the CAPS Registry from the European Forum on Antiphospholipid Antibodies. This international registry was set up in 2000 and has been assembling the clinical, laboratory, and therapeutic findings of patients with CAPS for almost 20 years.

“We observed 525 episodes of CAPS in 502 patients. That means that some patients had two to three episodes of CAPS,” Dr. Rodríguez-Pintó said. Data on 38 episodes of CAPS had to be excluded from the analysis because of missing information, which left 487 episodes occurring in 471 patients.

The mean age of the 471 patients included in the analysis was 38 years. The majority (67.9%) were female and had primary (68.8%) APS. Triple therapy was given to about 40% of patients who experienced CAPS, with about 57% receiving other combinations of drugs and 2.5% receiving no treatment for CAPS.

Overall, 177 of the 487 (36.3%) episodes of CAPS were fatal.

“Triple therapy was associated with a higher chance of survival when compared to other combinations or to none of these treatments,” Dr. Rodríguez-Pintó said.

While 28% of patients with CAPS died in the triple therapy group, mortality was 41% with other combinations of treatments and 75% with none of these treatments.

All-cause mortality was reduced by 47% with triple therapy, compared with none of these treatments. The adjusted odds ratio (aOR) when comparing survival between triple therapy and no treatment was 7.7, with a 95% confidence interval of 2.0 to 29.7. The aOR comparing other drug combinations versus none of these treatments was 6.8 (95% CI, 1.7-29.6).

“For a long time, we have been saying that triple therapy would probably be the best approach, but we had no firm evidence,” Dr. Rodríguez-Pintó said.

“So, this is the first time that we have clear clinical evidence of the benefit of these approaches, and I think that these results are important because they will give us more confidence in how we treat patients and help develop guidance on [the treatment’s] use in the future.”

Guidelines

A steering committee composed of representatives from the European Commission–funded RARE-BestPractices project and McMaster University in Hamilton, Ont., used GRADE methodology to develop the guidelines for CAPS diagnosis and management. The committee answered three diagnostic and seven treatment questions that originated from a panel of 19 international stakeholders, including Dr. Rodríguez-Pintó, through systematic reviews of the literature that used Cochrane criteria.

Although the review of studies did not include the study of CAPS Registry data that Dr. Rodríguez-Pintó and his colleagues conducted, he said that the recommendations still confirm the value of using a triple therapy approach to treatment.

The panel created three diagnostic recommendations for patients suspected of having CAPS, all of which were conditional and based on very low certainty of evidence: use preliminary CAPS classification criteria to diagnose CAPS; use or nonuse of biopsy, depending on the circumstances, because of its high specificity but possibly low sensitivity for thrombotic microangiopathy; and test for antiphospholipid antibodies, which should not delay initiation of treatment.

All seven first-line treatment recommendations that the panel developed relied on a very low certainty of evidence, and most were conditional:

• Triple therapy combination treatment with corticosteroids, heparin, and plasma exchange or intravenous immunoglobulins instead of a single agent or other combination treatments.
• Therapeutic dose anticoagulation was one of only two treatment recommendations to be considered “strong,” but use of direct oral anticoagulants is not advised.
• Therapeutic plasma exchange is recommended for use with other therapies and should be strongly considered for patients with microangiopathic hemolytic anemia.
• Intravenous immunoglobulin is advised for use in conjunction with other therapies and should be given special consideration for patients with immune thrombocytopenia or renal insufficiency.
• Antiplatelet agents are conditionally recommended as an add-on therapy, but their potential mortality benefit is tempered by increased risk of bleeding when used with anticoagulants. Strong consideration should be given to their use as an alternative therapy to anticoagulation when anticoagulation is contraindicated for a reason other than bleeding.
• Rituximab (Rituxan) should not be used because of little available data on its use, uncertainty regarding long-term consequences, and its expense – except for refractory cases where other therapies have been insufficient.
• Corticosteroids should not be used because of their lack of efficacy in CAPS when used alone and potential for adverse effects, except for certain circumstances where they may be indicated.

The authors of the guidelines emphasized that these recommendations are not meant to apply to every CAPS patient. They also noted that the available evidence did not allow for temporal analysis of treatments and that conclusions could not be drawn regarding “first-line” versus “second-line” therapies.

None of the authors of the registry study or the guidelines had relevant conflicts of interest to declare.

jevans@frontlinemedcom.com

MADRID – Catastrophic antiphospholipid syndrome (CAPS) is associated with a high mortality rate, but new research presented at the European Congress of Rheumatology shows that patient survival can be significantly improved by a triple therapy treatment approach.

Researchers at the Congress also presented clinical practice guidelines for the diagnosis and management of the rare disease, which accounts for just 1% of patients with antiphospholipid syndrome (APS).

CAPS is characterized by a fast onset of widespread thrombosis, mainly in the small vessels, and, often, microangiopathic hemolytic anemia is seen in the laboratory. If undiagnosed or left untreated, patients may present with multiorgan failure needing intensive care treatment, which can be fatal in up to 50% of cases.

At the Congress, Ignasi Rodríguez-Pintó, MD, presented new data from the CAPS Registry that looks at the combined effect of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins on the survival of patients with CAPS as well as the new clinical practice guidelines.

CAPS Registry study

The aim of the study Dr. Rodríguez-Pintó presented on behalf of the CAPS Registry Project Group was to determine what, if any, survival benefit would be incurred from a triple therapy approach when compared with other different combinations of anticoagulation, corticosteroids, and plasma exchange or intravenous immunoglobulins, or none of these treatments.

Although the triple therapy treatment approach is already being used in practice, its use is largely empirical, Dr. Rodríguez-Pintó of the department of autoimmune disease at the Hospital Clinic, Barcelona, explained in a video interview.

The investigators derived their data from episodes of CAPS occurring in patients in the CAPS Registry from the European Forum on Antiphospholipid Antibodies. This international registry was set up in 2000 and has been assembling the clinical, laboratory, and therapeutic findings of patients with CAPS for almost 20 years.

“We observed 525 episodes of CAPS in 502 patients. That means that some patients had two to three episodes of CAPS,” Dr. Rodríguez-Pintó said. Data on 38 episodes of CAPS had to be excluded from the analysis because of missing information, which left 487 episodes occurring in 471 patients.

The mean age of the 471 patients included in the analysis was 38 years. The majority (67.9%) were female and had primary (68.8%) APS. Triple therapy was given to about 40% of patients who experienced CAPS, with about 57% receiving other combinations of drugs and 2.5% receiving no treatment for CAPS.

Overall, 177 of the 487 (36.3%) episodes of CAPS were fatal.

“Triple therapy was associated with a higher chance of survival when compared to other combinations or to none of these treatments,” Dr. Rodríguez-Pintó said.

While 28% of patients with CAPS died in the triple therapy group, mortality was 41% with other combinations of treatments and 75% with none of these treatments.

All-cause mortality was reduced by 47% with triple therapy, compared with none of these treatments. The adjusted odds ratio (aOR) when comparing survival between triple therapy and no treatment was 7.7, with a 95% confidence interval of 2.0 to 29.7. The aOR comparing other drug combinations versus none of these treatments was 6.8 (95% CI, 1.7-29.6).

“For a long time, we have been saying that triple therapy would probably be the best approach, but we had no firm evidence,” Dr. Rodríguez-Pintó said.

“So, this is the first time that we have clear clinical evidence of the benefit of these approaches, and I think that these results are important because they will give us more confidence in how we treat patients and help develop guidance on [the treatment’s] use in the future.”

Guidelines

A steering committee composed of representatives from the European Commission–funded RARE-BestPractices project and McMaster University in Hamilton, Ont., used GRADE methodology to develop the guidelines for CAPS diagnosis and management. The committee answered three diagnostic and seven treatment questions that originated from a panel of 19 international stakeholders, including Dr. Rodríguez-Pintó, through systematic reviews of the literature that used Cochrane criteria.

Although the review of studies did not include the study of CAPS Registry data that Dr. Rodríguez-Pintó and his colleagues conducted, he said that the recommendations still confirm the value of using a triple therapy approach to treatment.

The panel created three diagnostic recommendations for patients suspected of having CAPS, all of which were conditional and based on very low certainty of evidence: use preliminary CAPS classification criteria to diagnose CAPS; use or nonuse of biopsy, depending on the circumstances, because of its high specificity but possibly low sensitivity for thrombotic microangiopathy; and test for antiphospholipid antibodies, which should not delay initiation of treatment.

All seven first-line treatment recommendations that the panel developed relied on a very low certainty of evidence, and most were conditional:

• Triple therapy combination treatment with corticosteroids, heparin, and plasma exchange or intravenous immunoglobulins instead of a single agent or other combination treatments.
• Therapeutic dose anticoagulation was one of only two treatment recommendations to be considered “strong,” but use of direct oral anticoagulants is not advised.
• Therapeutic plasma exchange is recommended for use with other therapies and should be strongly considered for patients with microangiopathic hemolytic anemia.
• Intravenous immunoglobulin is advised for use in conjunction with other therapies and should be given special consideration for patients with immune thrombocytopenia or renal insufficiency.
• Antiplatelet agents are conditionally recommended as an add-on therapy, but their potential mortality benefit is tempered by increased risk of bleeding when used with anticoagulants. Strong consideration should be given to their use as an alternative therapy to anticoagulation when anticoagulation is contraindicated for a reason other than bleeding.
• Rituximab (Rituxan) should not be used because of little available data on its use, uncertainty regarding long-term consequences, and its expense – except for refractory cases where other therapies have been insufficient.
• Corticosteroids should not be used because of their lack of efficacy in CAPS when used alone and potential for adverse effects, except for certain circumstances where they may be indicated.

The authors of the guidelines emphasized that these recommendations are not meant to apply to every CAPS patient. They also noted that the available evidence did not allow for temporal analysis of treatments and that conclusions could not be drawn regarding “first-line” versus “second-line” therapies.

None of the authors of the registry study or the guidelines had relevant conflicts of interest to declare.

jevans@frontlinemedcom.com

BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.

Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.

“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.

But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.

“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”

A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).

Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.

A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.

Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.

The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.

Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.

“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.

But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.

“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”

A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).

Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.

A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.

Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.

The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

BOSTON – Lenvatinib’s real-world performance treating advanced, radio-iodine refractory, differentiated thyroid cancer closely followed the efficacy and adverse effect profiles the drug showed in its pivotal trial.

Lenvatinib showed good efficacy in 75 French registry patients, while also producing adverse effects in virtually every patient, but with the possibility to resolve the adverse effects with dose reductions or short-term treatment discontinuations, Martin Schlumberger, MD, said at the World Congress on Thyroid Cancer.

“Lenvatinib is toxic, but the toxicity can be managed in almost all patients by drug withholding or by reducing the dosage, and with symptomatic treatments,” Dr. Schlumberger said in a video interview. But adverse events are a “major problem” for the drug, so patients receiving lenvatinib “should be seen very frequently, and as soon as toxicity appears it should be treated,” said Dr. Schlumberger, professor of medicine and chairman of nuclear medicine and endocrine oncology at Gustave Roussy in Paris.

But lenvatinib’s efficacy makes it a first-line option despite the frequent adverse effects it causes.

“Without doubt it is the most effective drug” for treating advanced, rapidly progressing, radio-iodine refractory thyroid cancer, he said. “When patients really need systemic therapy they should get lenvatinib. It’s a balance of risk and benefit, and the risk from not being treated is higher than the risk from adverse effects.”

A similar pattern of adverse effects and efficacy was seen for lenvatinib in the pivotal Study of Lenvatinib in Differentiated Cancer of the Thyroid (SELECT) trial, which reported a median 18-month progression-free survival rate among patients treated with the drug compared with a median 4-month progression-free survival rate in placebo-treated patients (N Engl J Med. 2015 Feb 12;372[7]:621-30).

Among the 75 patients enrolled in the French registry, the median time of progression-free survival was 10 months, with 8 patients on continued therapy without progression. The response rate in the registry was 31% compared with 65% in the SELECT trial (and 2% in placebo-treated patients in SELECT), but the registry included many patients with advanced disease, comorbidities, and pretreatment, Dr. Schlumberger reported. Just 17 of the registry patients (23%) would have met the enrollment criteria for SELECT. Among this subset the response rate to lenvatinib was 47%.

A multivariate analysis identified three factors that significantly linked with drug responses, Dr. Schlumberger said: pretreatment, more advanced disease, and comorbidities.

Treatment-related adverse effects occurred in 71 of the registry patients (95%), with half of these grade 3 or higher. Twelve patients (16%) discontinued treatment because of an adverse effect. Hypertension was the most common adverse effect, occurring in 50 patients (67%), with 26 having grade 3 or higher hypertension. Other common adverse effects were fatigue, weight loss, diarrhea, and anorexia.

The 75 patients began treatment with lenvatinib for advanced thyroid cancer at any of 24 French centers during April 2015–June 2016. This marked the first year when lenvatinib was available in France for routine use, which roughly coincided with its U.S. introduction after lenvatinib received Food and Drug Administration marketing approval for advanced thyroid cancer in February 2015. Fifty-four patients (72%) began treatment on the labeled dosage of 24 mg/day; the remaining patients started the drug at a lower dosage.

mzoler@frontlinemedcom.com

On Twitter @mitchelzoler

SAN DIEGO – Researchers are looking at the potential role that autoimmune reactions, such as inflammation, play in the pathogenesis of schizophrenia, both with and without comorbid substance use.

“What we see is evidence of autoimmune involvement through the lifespan in schizophrenia,” explained Brian Miller, MD, PhD, of the department of psychiatry at Augusta (Georgia) University. “We know there is a bidirectional association between schizophrenia and autoimmune disorders, [where] starting with either increases the chances of the other occurring comorbidly.”

Previous studies have shown that adding anti-inflammatory agents to second-generation antipsychotics has been associated with greater symptomatic improvement in schizophrenia than with second-generation antipsychotics alone. Now, Dr. Miller and his colleagues are conducting a randomized, controlled study using the systemic immunotherapy siltuximab to see if adjunct anti-inflammatory treatments can improve cognition in schizophrenia. They are using the monoclonal antibody instead of nonsteroidal anti-inflammatory drugs because of its precise ability to target specific autoimmune pathways, according to Dr. Miller.

In addition, Dr. Miller and his colleagues conducted a post-hoc analysis of data from the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study to determine if there was a difference between those patients with comorbid substance in schizophrenia, compared with those without. He and his coinvestigators found in a post-hoc analysis that the higher the level of certain inflammatory markers, the higher the Positive and Negative Syndrome Scale (PANSS) psychopathology score in people who’d tested positive for marijuana use at baseline.

The results, he said, beg the question about whether trial inclusion criteria for schizophrenia research need revisiting.

“What we really need to do is investigate, in a well-controlled, well-designed, prospective sample of patients who have this substance use comorbidity, [whether] we see alterations in these immune markers, and then how they vary over the course of illness,” Dr. Miller explained in a video interview at the International Congress on Schizophrenia Research. “It’s an important selection bias that as a field we’ve ignored. Maybe that’s a population that is enriched for some kind of immune dysfunction that might be targeted by some kind of anti-inflammatory or other immunotherapy strategy.”

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight
 

SAN DIEGO – Researchers are looking at the potential role that autoimmune reactions, such as inflammation, play in the pathogenesis of schizophrenia, both with and without comorbid substance use.

“What we see is evidence of autoimmune involvement through the lifespan in schizophrenia,” explained Brian Miller, MD, PhD, of the department of psychiatry at Augusta (Georgia) University. “We know there is a bidirectional association between schizophrenia and autoimmune disorders, [where] starting with either increases the chances of the other occurring comorbidly.”

Previous studies have shown that adding anti-inflammatory agents to second-generation antipsychotics has been associated with greater symptomatic improvement in schizophrenia than with second-generation antipsychotics alone. Now, Dr. Miller and his colleagues are conducting a randomized, controlled study using the systemic immunotherapy siltuximab to see if adjunct anti-inflammatory treatments can improve cognition in schizophrenia. They are using the monoclonal antibody instead of nonsteroidal anti-inflammatory drugs because of its precise ability to target specific autoimmune pathways, according to Dr. Miller.

In addition, Dr. Miller and his colleagues conducted a post-hoc analysis of data from the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study to determine if there was a difference between those patients with comorbid substance in schizophrenia, compared with those without. He and his coinvestigators found in a post-hoc analysis that the higher the level of certain inflammatory markers, the higher the Positive and Negative Syndrome Scale (PANSS) psychopathology score in people who’d tested positive for marijuana use at baseline.

The results, he said, beg the question about whether trial inclusion criteria for schizophrenia research need revisiting.

“What we really need to do is investigate, in a well-controlled, well-designed, prospective sample of patients who have this substance use comorbidity, [whether] we see alterations in these immune markers, and then how they vary over the course of illness,” Dr. Miller explained in a video interview at the International Congress on Schizophrenia Research. “It’s an important selection bias that as a field we’ve ignored. Maybe that’s a population that is enriched for some kind of immune dysfunction that might be targeted by some kind of anti-inflammatory or other immunotherapy strategy.”

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight
 

SAN DIEGO – Researchers are looking at the potential role that autoimmune reactions, such as inflammation, play in the pathogenesis of schizophrenia, both with and without comorbid substance use.

“What we see is evidence of autoimmune involvement through the lifespan in schizophrenia,” explained Brian Miller, MD, PhD, of the department of psychiatry at Augusta (Georgia) University. “We know there is a bidirectional association between schizophrenia and autoimmune disorders, [where] starting with either increases the chances of the other occurring comorbidly.”

Previous studies have shown that adding anti-inflammatory agents to second-generation antipsychotics has been associated with greater symptomatic improvement in schizophrenia than with second-generation antipsychotics alone. Now, Dr. Miller and his colleagues are conducting a randomized, controlled study using the systemic immunotherapy siltuximab to see if adjunct anti-inflammatory treatments can improve cognition in schizophrenia. They are using the monoclonal antibody instead of nonsteroidal anti-inflammatory drugs because of its precise ability to target specific autoimmune pathways, according to Dr. Miller.

In addition, Dr. Miller and his colleagues conducted a post-hoc analysis of data from the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study to determine if there was a difference between those patients with comorbid substance in schizophrenia, compared with those without. He and his coinvestigators found in a post-hoc analysis that the higher the level of certain inflammatory markers, the higher the Positive and Negative Syndrome Scale (PANSS) psychopathology score in people who’d tested positive for marijuana use at baseline.

The results, he said, beg the question about whether trial inclusion criteria for schizophrenia research need revisiting.

“What we really need to do is investigate, in a well-controlled, well-designed, prospective sample of patients who have this substance use comorbidity, [whether] we see alterations in these immune markers, and then how they vary over the course of illness,” Dr. Miller explained in a video interview at the International Congress on Schizophrenia Research. “It’s an important selection bias that as a field we’ve ignored. Maybe that’s a population that is enriched for some kind of immune dysfunction that might be targeted by some kind of anti-inflammatory or other immunotherapy strategy.”

wmcknight@frontlinemedcom.com

On Twitter @whitneymcknight
 

Almost half of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) did not undergo cholecystectomy (CCY) within the next 60 days according to the results of a large, retrospective cohort study reported in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2017.05.048).

“Although early and delayed CCY equally reduce the risk of subsequent recurrent biliary events, patients are at 10-fold higher risk of a recurrent biliary event while waiting for a delayed CCY, compared with patients who underwent early CCY,” wrote Robert J. Huang, MD, and his associates of Stanford (Calif.) University Medical Center. Delayed CCY is cost effective, but that benefit must be weighed against the risk of loss to follow-up, especially if patients have “little or no health insurance,” they said.

Source: American Gastroenterological Association

Gallstone disease affects up to 15% of adults in developed societies, including about 20-25 million Americans. Yearly costs of treatment tally at more than $6.2 billion and have risen by more than 20% in 3 decades, according to multiple studies. Approximately 20% of patients with gallstone disease have choledocholithiasis, mainly because gallstones can pass from the gallbladder into the common bile duct. After undergoing ERCP, such patients are typically referred for CCY, but there are no “societal guidelines” on timing the referral, the researchers said. Practice patterns remain “largely institution based and may be subject to the vagaries of surgeon availability and other institutional resource constraints.” One prior study linked a median 7-week wait time for CCY with a 20% rate of recurrent biliary events. To evaluate large-scale practice patterns, the researchers studied 4,516 patients who had undergone ERCP for choledocholithiasis in California (during 2009-2011), New York (during 2011-2013), and Florida (during 2012-2014) and calculated timing and rates of subsequent CCY, recurrent biliary events, and deaths. Patients were followed for up to 365 days after ERCP.

Of the 4,516 patients studied, 1,859 (41.2%) patients underwent CCY during their index hospital admission (early CCY). Of the 2,657 (58.8%) patients who were discharged without CCY, only 491 (18%) had a planned CCY within 60 days (delayed CCY), 350 (71.3%) of which were done in an outpatient setting. Of the patients in the study, 2,168 (48.0%) did not have a CCY (no CCY) during their index visit or within 60 days. Over 365 days of follow-up, 10% of patients who did not have a CCY had recurrent biliary events, compared with 1.3% of patients who underwent early or delayed CCY. The risk of recurrent biliary events for patients who underwent early or delayed CCY was about 88% lower than if they had had no CCY within 60 days of ERCP (P less than .001 for each comparison). Performing CCY during index admission cut the risk of recurrent biliary events occurring within 60 days by 92%, compared with delayed or no CCY (P less than .001).

In all, 15 (0.7%) patients who did not undergo CCY died after subsequent hospitalization for a recurrent biliary event, compared with 1 patient who underwent early CCY (0.1%; P less than .001). There were no deaths associated with recurrent biliary events in the delayed-CCY group. Rates of all-cause mortality over 365 days were 3.1% in the no-CCY group, 0.6% in the early-CCY group, and 0% in the delayed-CCY group. Thus, cumulative death rates were about seven times higher among patients who did not undergo CCY compared with those who did (P less than .001).

Patients who did not undergo CCY tended to be older than delayed- and early-CCY patients (mean ages 66 years, 58 years, and 52 years, respectively). No-CCY patients also tended to have more comorbidities. Nonetheless, having an early CCY retained a “robust” protective effect against recurrent biliary events after accounting for age, sex, comorbidities, stent placement, facility volume, and state of residence. Even after researchers adjusted for those factors, the protective effect of early CCY dropped by less than 5% (from 92% to about 87%), the investigators said.

They also noted that the overall cohort averaged 60 years of age and that 64% were female, which is consistent with the epidemiology of biliary stone disease. Just over half were non-Hispanic whites. Medicare was the single largest primary payer (46%), followed by private insurance (28%) and Medicaid (16%).

“A strategy of delayed CCY performed on an outpatient basis was least costly,” the researchers said. “Performance of early CCY was inversely associated with low facility volume. Hispanic race, Asian race, Medicaid insurance, and no insurance associated inversely with performance of delayed CCY.”

Funders included a seed grant from the Stanford division of gastroenterology and hepatology and the National Institutes of Health. The investigators had no conflicts of interest.

Almost half of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) did not undergo cholecystectomy (CCY) within the next 60 days according to the results of a large, retrospective cohort study reported in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2017.05.048).

“Although early and delayed CCY equally reduce the risk of subsequent recurrent biliary events, patients are at 10-fold higher risk of a recurrent biliary event while waiting for a delayed CCY, compared with patients who underwent early CCY,” wrote Robert J. Huang, MD, and his associates of Stanford (Calif.) University Medical Center. Delayed CCY is cost effective, but that benefit must be weighed against the risk of loss to follow-up, especially if patients have “little or no health insurance,” they said.

Source: American Gastroenterological Association

Gallstone disease affects up to 15% of adults in developed societies, including about 20-25 million Americans. Yearly costs of treatment tally at more than $6.2 billion and have risen by more than 20% in 3 decades, according to multiple studies. Approximately 20% of patients with gallstone disease have choledocholithiasis, mainly because gallstones can pass from the gallbladder into the common bile duct. After undergoing ERCP, such patients are typically referred for CCY, but there are no “societal guidelines” on timing the referral, the researchers said. Practice patterns remain “largely institution based and may be subject to the vagaries of surgeon availability and other institutional resource constraints.” One prior study linked a median 7-week wait time for CCY with a 20% rate of recurrent biliary events. To evaluate large-scale practice patterns, the researchers studied 4,516 patients who had undergone ERCP for choledocholithiasis in California (during 2009-2011), New York (during 2011-2013), and Florida (during 2012-2014) and calculated timing and rates of subsequent CCY, recurrent biliary events, and deaths. Patients were followed for up to 365 days after ERCP.

Of the 4,516 patients studied, 1,859 (41.2%) patients underwent CCY during their index hospital admission (early CCY). Of the 2,657 (58.8%) patients who were discharged without CCY, only 491 (18%) had a planned CCY within 60 days (delayed CCY), 350 (71.3%) of which were done in an outpatient setting. Of the patients in the study, 2,168 (48.0%) did not have a CCY (no CCY) during their index visit or within 60 days. Over 365 days of follow-up, 10% of patients who did not have a CCY had recurrent biliary events, compared with 1.3% of patients who underwent early or delayed CCY. The risk of recurrent biliary events for patients who underwent early or delayed CCY was about 88% lower than if they had had no CCY within 60 days of ERCP (P less than .001 for each comparison). Performing CCY during index admission cut the risk of recurrent biliary events occurring within 60 days by 92%, compared with delayed or no CCY (P less than .001).

In all, 15 (0.7%) patients who did not undergo CCY died after subsequent hospitalization for a recurrent biliary event, compared with 1 patient who underwent early CCY (0.1%; P less than .001). There were no deaths associated with recurrent biliary events in the delayed-CCY group. Rates of all-cause mortality over 365 days were 3.1% in the no-CCY group, 0.6% in the early-CCY group, and 0% in the delayed-CCY group. Thus, cumulative death rates were about seven times higher among patients who did not undergo CCY compared with those who did (P less than .001).

Patients who did not undergo CCY tended to be older than delayed- and early-CCY patients (mean ages 66 years, 58 years, and 52 years, respectively). No-CCY patients also tended to have more comorbidities. Nonetheless, having an early CCY retained a “robust” protective effect against recurrent biliary events after accounting for age, sex, comorbidities, stent placement, facility volume, and state of residence. Even after researchers adjusted for those factors, the protective effect of early CCY dropped by less than 5% (from 92% to about 87%), the investigators said.

They also noted that the overall cohort averaged 60 years of age and that 64% were female, which is consistent with the epidemiology of biliary stone disease. Just over half were non-Hispanic whites. Medicare was the single largest primary payer (46%), followed by private insurance (28%) and Medicaid (16%).

“A strategy of delayed CCY performed on an outpatient basis was least costly,” the researchers said. “Performance of early CCY was inversely associated with low facility volume. Hispanic race, Asian race, Medicaid insurance, and no insurance associated inversely with performance of delayed CCY.”

Funders included a seed grant from the Stanford division of gastroenterology and hepatology and the National Institutes of Health. The investigators had no conflicts of interest.

Almost half of patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) did not undergo cholecystectomy (CCY) within the next 60 days according to the results of a large, retrospective cohort study reported in the September issue of Gastroenterology (doi: 10.1053/j.gastro.2017.05.048).

“Although early and delayed CCY equally reduce the risk of subsequent recurrent biliary events, patients are at 10-fold higher risk of a recurrent biliary event while waiting for a delayed CCY, compared with patients who underwent early CCY,” wrote Robert J. Huang, MD, and his associates of Stanford (Calif.) University Medical Center. Delayed CCY is cost effective, but that benefit must be weighed against the risk of loss to follow-up, especially if patients have “little or no health insurance,” they said.

Source: American Gastroenterological Association

Gallstone disease affects up to 15% of adults in developed societies, including about 20-25 million Americans. Yearly costs of treatment tally at more than $6.2 billion and have risen by more than 20% in 3 decades, according to multiple studies. Approximately 20% of patients with gallstone disease have choledocholithiasis, mainly because gallstones can pass from the gallbladder into the common bile duct. After undergoing ERCP, such patients are typically referred for CCY, but there are no “societal guidelines” on timing the referral, the researchers said. Practice patterns remain “largely institution based and may be subject to the vagaries of surgeon availability and other institutional resource constraints.” One prior study linked a median 7-week wait time for CCY with a 20% rate of recurrent biliary events. To evaluate large-scale practice patterns, the researchers studied 4,516 patients who had undergone ERCP for choledocholithiasis in California (during 2009-2011), New York (during 2011-2013), and Florida (during 2012-2014) and calculated timing and rates of subsequent CCY, recurrent biliary events, and deaths. Patients were followed for up to 365 days after ERCP.

Of the 4,516 patients studied, 1,859 (41.2%) patients underwent CCY during their index hospital admission (early CCY). Of the 2,657 (58.8%) patients who were discharged without CCY, only 491 (18%) had a planned CCY within 60 days (delayed CCY), 350 (71.3%) of which were done in an outpatient setting. Of the patients in the study, 2,168 (48.0%) did not have a CCY (no CCY) during their index visit or within 60 days. Over 365 days of follow-up, 10% of patients who did not have a CCY had recurrent biliary events, compared with 1.3% of patients who underwent early or delayed CCY. The risk of recurrent biliary events for patients who underwent early or delayed CCY was about 88% lower than if they had had no CCY within 60 days of ERCP (P less than .001 for each comparison). Performing CCY during index admission cut the risk of recurrent biliary events occurring within 60 days by 92%, compared with delayed or no CCY (P less than .001).

In all, 15 (0.7%) patients who did not undergo CCY died after subsequent hospitalization for a recurrent biliary event, compared with 1 patient who underwent early CCY (0.1%; P less than .001). There were no deaths associated with recurrent biliary events in the delayed-CCY group. Rates of all-cause mortality over 365 days were 3.1% in the no-CCY group, 0.6% in the early-CCY group, and 0% in the delayed-CCY group. Thus, cumulative death rates were about seven times higher among patients who did not undergo CCY compared with those who did (P less than .001).

Patients who did not undergo CCY tended to be older than delayed- and early-CCY patients (mean ages 66 years, 58 years, and 52 years, respectively). No-CCY patients also tended to have more comorbidities. Nonetheless, having an early CCY retained a “robust” protective effect against recurrent biliary events after accounting for age, sex, comorbidities, stent placement, facility volume, and state of residence. Even after researchers adjusted for those factors, the protective effect of early CCY dropped by less than 5% (from 92% to about 87%), the investigators said.

They also noted that the overall cohort averaged 60 years of age and that 64% were female, which is consistent with the epidemiology of biliary stone disease. Just over half were non-Hispanic whites. Medicare was the single largest primary payer (46%), followed by private insurance (28%) and Medicaid (16%).

“A strategy of delayed CCY performed on an outpatient basis was least costly,” the researchers said. “Performance of early CCY was inversely associated with low facility volume. Hispanic race, Asian race, Medicaid insurance, and no insurance associated inversely with performance of delayed CCY.”

Funders included a seed grant from the Stanford division of gastroenterology and hepatology and the National Institutes of Health. The investigators had no conflicts of interest.