ORLANDO – A gamma secretase inhibitor could enhance the efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma, a phase 1 trial suggests.

Jennifer Smith/MDedge News

The inhibitor, JSMD194, increased BCMA expression in all 10 patients studied. All patients responded to anti-BCMA CAR T-cell therapy, including three patients who had previously failed BCMA-directed therapy.

Nine patients remain alive and in response at a median follow-up of 20 weeks, with two patients being followed for more than a year. One patient experienced dose-limiting toxicity and died, which prompted a change to the study’s eligibility criteria.

Andrew J. Cowan, MD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, presented these results at the annual meeting of the American Society of Hematology.

Study treatment

Patients had BCMA expression measured at baseline, then underwent apheresis for CAR T-cell production.

Patients received JSMD194 at 25 mg on days 1, 3, and 5. Then, they received cyclophosphamide at 300 mg and fludarabine at 25 mg for 3 days.

Next, patients received a single CAR T-cell infusion at a dose of 50 x 10⁶ (n = 5), 150 x 10⁶ (n = 3), or 300 x 10⁶ (n = 2). They also received JSMD194 at 25 mg three times a week for 3 weeks.

Safety

“Nearly all patients had a serious adverse event, which was typically admission to the hospital for neutropenic fever,” Dr. Cowan said.

One patient experienced dose-limiting toxicity and died at day 33. The patient had a disseminating fungal infection, grade 4 cytokine release syndrome (CRS), and neurotoxicity. The patient’s death prompted the researchers to include performance status in the study’s eligibility criteria.

All patients developed CRS. Only the aforementioned patient had grade 4 CRS, and three patients had grade 3 CRS. Six patients experienced neurotoxicity. There were no cases of tumor lysis syndrome.
 

Efficacy

“All patients experienced an increase of cells expressing BCMA,” Dr. Cowan said. “While there was significant variability in BCMA expression at baseline, all cells expressed BCMA after three doses of the gamma secretase inhibitor.”

The median BCMA expression after JSMD194 treatment was 99% (range, 96%-100%), and there was a median 20-fold (range, 8- to 157-fold) increase in BCMA surface density.

The overall response rate was 100%. Two patients achieved a stringent complete response (CR), one achieved a CR, five patients had a very good partial response, and two had a partial response.

The patient with a CR received the 50 x 10⁶ dose of CAR T cells, and the patients with stringent CRs received the 150 x 10⁶ and 300 x 10⁶ doses.

Of the three patients who previously received BCMA-directed therapy, two achieved a very good partial response, and one had a partial response.

Nine of the 10 patients are still alive and in response, with a median follow-up of 20 weeks. The longest follow-up is 444 days.

“To date, all patients have evidence of durable responses,” Dr. Cowan said. “Moreover, all patients had dramatic reductions in involved serum free light chain ... and serum monoclonal proteins.”

Dr. Cowan noted that longer follow-up is needed to assess CAR T-cell persistence and the durability of response.

This trial is sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. Two researchers involved in this work are employees of Juno Therapeutics. Dr. Cowan reported relationships with Juno Therapeutics, Janssen, Celgene, AbbVie, Cellectar, and Sanofi.

[email protected]

SOURCE: Cowan AJ et al. ASH 2019. Abstract 204.

ORLANDO – A gamma secretase inhibitor could enhance the efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma, a phase 1 trial suggests.

Jennifer Smith/MDedge News

The inhibitor, JSMD194, increased BCMA expression in all 10 patients studied. All patients responded to anti-BCMA CAR T-cell therapy, including three patients who had previously failed BCMA-directed therapy.

Nine patients remain alive and in response at a median follow-up of 20 weeks, with two patients being followed for more than a year. One patient experienced dose-limiting toxicity and died, which prompted a change to the study’s eligibility criteria.

Andrew J. Cowan, MD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, presented these results at the annual meeting of the American Society of Hematology.

Study treatment

Patients had BCMA expression measured at baseline, then underwent apheresis for CAR T-cell production.

Patients received JSMD194 at 25 mg on days 1, 3, and 5. Then, they received cyclophosphamide at 300 mg and fludarabine at 25 mg for 3 days.

Next, patients received a single CAR T-cell infusion at a dose of 50 x 10⁶ (n = 5), 150 x 10⁶ (n = 3), or 300 x 10⁶ (n = 2). They also received JSMD194 at 25 mg three times a week for 3 weeks.

Safety

“Nearly all patients had a serious adverse event, which was typically admission to the hospital for neutropenic fever,” Dr. Cowan said.

One patient experienced dose-limiting toxicity and died at day 33. The patient had a disseminating fungal infection, grade 4 cytokine release syndrome (CRS), and neurotoxicity. The patient’s death prompted the researchers to include performance status in the study’s eligibility criteria.

All patients developed CRS. Only the aforementioned patient had grade 4 CRS, and three patients had grade 3 CRS. Six patients experienced neurotoxicity. There were no cases of tumor lysis syndrome.
 

Efficacy

“All patients experienced an increase of cells expressing BCMA,” Dr. Cowan said. “While there was significant variability in BCMA expression at baseline, all cells expressed BCMA after three doses of the gamma secretase inhibitor.”

The median BCMA expression after JSMD194 treatment was 99% (range, 96%-100%), and there was a median 20-fold (range, 8- to 157-fold) increase in BCMA surface density.

The overall response rate was 100%. Two patients achieved a stringent complete response (CR), one achieved a CR, five patients had a very good partial response, and two had a partial response.

The patient with a CR received the 50 x 10⁶ dose of CAR T cells, and the patients with stringent CRs received the 150 x 10⁶ and 300 x 10⁶ doses.

Of the three patients who previously received BCMA-directed therapy, two achieved a very good partial response, and one had a partial response.

Nine of the 10 patients are still alive and in response, with a median follow-up of 20 weeks. The longest follow-up is 444 days.

“To date, all patients have evidence of durable responses,” Dr. Cowan said. “Moreover, all patients had dramatic reductions in involved serum free light chain ... and serum monoclonal proteins.”

Dr. Cowan noted that longer follow-up is needed to assess CAR T-cell persistence and the durability of response.

This trial is sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. Two researchers involved in this work are employees of Juno Therapeutics. Dr. Cowan reported relationships with Juno Therapeutics, Janssen, Celgene, AbbVie, Cellectar, and Sanofi.

[email protected]

SOURCE: Cowan AJ et al. ASH 2019. Abstract 204.

ORLANDO – A gamma secretase inhibitor could enhance the efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cells in patients with relapsed or refractory multiple myeloma, a phase 1 trial suggests.

Jennifer Smith/MDedge News

The inhibitor, JSMD194, increased BCMA expression in all 10 patients studied. All patients responded to anti-BCMA CAR T-cell therapy, including three patients who had previously failed BCMA-directed therapy.

Nine patients remain alive and in response at a median follow-up of 20 weeks, with two patients being followed for more than a year. One patient experienced dose-limiting toxicity and died, which prompted a change to the study’s eligibility criteria.

Andrew J. Cowan, MD, of the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, presented these results at the annual meeting of the American Society of Hematology.

Study treatment

Patients had BCMA expression measured at baseline, then underwent apheresis for CAR T-cell production.

Patients received JSMD194 at 25 mg on days 1, 3, and 5. Then, they received cyclophosphamide at 300 mg and fludarabine at 25 mg for 3 days.

Next, patients received a single CAR T-cell infusion at a dose of 50 x 10⁶ (n = 5), 150 x 10⁶ (n = 3), or 300 x 10⁶ (n = 2). They also received JSMD194 at 25 mg three times a week for 3 weeks.

Safety

“Nearly all patients had a serious adverse event, which was typically admission to the hospital for neutropenic fever,” Dr. Cowan said.

One patient experienced dose-limiting toxicity and died at day 33. The patient had a disseminating fungal infection, grade 4 cytokine release syndrome (CRS), and neurotoxicity. The patient’s death prompted the researchers to include performance status in the study’s eligibility criteria.

All patients developed CRS. Only the aforementioned patient had grade 4 CRS, and three patients had grade 3 CRS. Six patients experienced neurotoxicity. There were no cases of tumor lysis syndrome.
 

Efficacy

“All patients experienced an increase of cells expressing BCMA,” Dr. Cowan said. “While there was significant variability in BCMA expression at baseline, all cells expressed BCMA after three doses of the gamma secretase inhibitor.”

The median BCMA expression after JSMD194 treatment was 99% (range, 96%-100%), and there was a median 20-fold (range, 8- to 157-fold) increase in BCMA surface density.

The overall response rate was 100%. Two patients achieved a stringent complete response (CR), one achieved a CR, five patients had a very good partial response, and two had a partial response.

The patient with a CR received the 50 x 10⁶ dose of CAR T cells, and the patients with stringent CRs received the 150 x 10⁶ and 300 x 10⁶ doses.

Of the three patients who previously received BCMA-directed therapy, two achieved a very good partial response, and one had a partial response.

Nine of the 10 patients are still alive and in response, with a median follow-up of 20 weeks. The longest follow-up is 444 days.

“To date, all patients have evidence of durable responses,” Dr. Cowan said. “Moreover, all patients had dramatic reductions in involved serum free light chain ... and serum monoclonal proteins.”

Dr. Cowan noted that longer follow-up is needed to assess CAR T-cell persistence and the durability of response.

This trial is sponsored by the Fred Hutchinson Cancer Research Center in collaboration with the National Cancer Institute. Two researchers involved in this work are employees of Juno Therapeutics. Dr. Cowan reported relationships with Juno Therapeutics, Janssen, Celgene, AbbVie, Cellectar, and Sanofi.

[email protected]

SOURCE: Cowan AJ et al. ASH 2019. Abstract 204.

Read Now.

The diagnosis of spinal muscular atrophy (SMA), especially Type 1, is a medical emergency, as SMA is a leading genetic cause of death in infants. In infants with SMA Type 1, the onset of irreversible denervation occurs within the first 3 months with loss of 90% of motor units occurring within 6 months of age.

This supplement examines the clinical implications of delayed diagnosis of SMA, as well as assessment tools, treatment methods, and resources that are available for physicians, patients, and caregivers to better manage this rare disease.

Read Now.

Read Now.

The diagnosis of spinal muscular atrophy (SMA), especially Type 1, is a medical emergency, as SMA is a leading genetic cause of death in infants. In infants with SMA Type 1, the onset of irreversible denervation occurs within the first 3 months with loss of 90% of motor units occurring within 6 months of age.

This supplement examines the clinical implications of delayed diagnosis of SMA, as well as assessment tools, treatment methods, and resources that are available for physicians, patients, and caregivers to better manage this rare disease.

Read Now.

Read Now.

The diagnosis of spinal muscular atrophy (SMA), especially Type 1, is a medical emergency, as SMA is a leading genetic cause of death in infants. In infants with SMA Type 1, the onset of irreversible denervation occurs within the first 3 months with loss of 90% of motor units occurring within 6 months of age.

This supplement examines the clinical implications of delayed diagnosis of SMA, as well as assessment tools, treatment methods, and resources that are available for physicians, patients, and caregivers to better manage this rare disease.

Read Now.

The Food and Drug Administration has approved lumateperone for the treatment of schizophrenia in adults.

Lumateperone, an atypical antipsychotic, will be marketed by Intra-Cellular Therapies as Caplyta, according to a Dec. 23 statement from the company.

Approval of the drug was based on two placebo-controlled trials. In the first, 335 patients with schizophrenia were randomized to two doses of lumateperone, an active comparator, or placebo. Those randomized to the approved 42-mg dose of lumateperone showed a statistically significant reduction in total score on the Positive and Negative Syndrome Scale (PANSS), compared with patients in the other groups. The median age in this study was 42 years; 17% of patients were female, 19% were white, and 78% were black.

In the second study, 450 patients diagnosed with schizophrenia were randomized in a double-blind fashion to one of two doses of lumateperone or placebo. Patients taking the approved dose showed a statistically significant reduction from baseline to day 28 in PANSS total score. In this study, patients’ median age was 44 years; 23% were female, 26% were white, and 66% were black.

Treatment with lumateperone appears to feature a more favorable cardiometabolic profile than that of other approved antipsychotic agents.

Patients treated with lumateperone for at least a year showed significant reductions in LDL cholesterol, total cholesterol, serum prolactin, and body weight, compared with baseline values recorded when participants were on various standard-of-care antipsychotics prior to switching, Suresh Durgam, MD, reported at the annual congress of the European College of Neuropsychopharmacology. Other cardiometabolic parameters, including fasting blood glucose, insulin, triglycerides, and HDL cholesterol, showed only negligible change over the course of study, according to Dr. Durgam, a psychiatrist and senior vice president for late-stage clinical development and medical affairs at Intra-Cellular Therapies.

The most common adverse events with lumateperone were somnolence (24% vs. 10% on placebo) and dry mouth (6% vs. 2%).

Approval of lumateperone hit a snag last summer when the FDA canceled the Psychopharmacologic Drugs Advisory Committee meeting it previously had called for to review the new drug application for lumateperone. The agency said the meeting was canceled because of “new information regarding the application.”

At the time, Intra-Cellular Therapies noted that it had provided additional information to the FDA to meet agency requests. This information was related to nonclinical studies.

“The FDA canceled the advisory committee meeting to allow sufficient time to review this new and any forthcoming information as they continue” to review the new drug application for lumateperone, Intra-Cellular said a statement.

The company plans to launch Caplyta late in the first quarter of 2020.

[email protected]

Bruce Jancin and Kerry Dooley Young contributed to this report.

The Food and Drug Administration has approved lumateperone for the treatment of schizophrenia in adults.

Lumateperone, an atypical antipsychotic, will be marketed by Intra-Cellular Therapies as Caplyta, according to a Dec. 23 statement from the company.

Approval of the drug was based on two placebo-controlled trials. In the first, 335 patients with schizophrenia were randomized to two doses of lumateperone, an active comparator, or placebo. Those randomized to the approved 42-mg dose of lumateperone showed a statistically significant reduction in total score on the Positive and Negative Syndrome Scale (PANSS), compared with patients in the other groups. The median age in this study was 42 years; 17% of patients were female, 19% were white, and 78% were black.

In the second study, 450 patients diagnosed with schizophrenia were randomized in a double-blind fashion to one of two doses of lumateperone or placebo. Patients taking the approved dose showed a statistically significant reduction from baseline to day 28 in PANSS total score. In this study, patients’ median age was 44 years; 23% were female, 26% were white, and 66% were black.

Treatment with lumateperone appears to feature a more favorable cardiometabolic profile than that of other approved antipsychotic agents.

Patients treated with lumateperone for at least a year showed significant reductions in LDL cholesterol, total cholesterol, serum prolactin, and body weight, compared with baseline values recorded when participants were on various standard-of-care antipsychotics prior to switching, Suresh Durgam, MD, reported at the annual congress of the European College of Neuropsychopharmacology. Other cardiometabolic parameters, including fasting blood glucose, insulin, triglycerides, and HDL cholesterol, showed only negligible change over the course of study, according to Dr. Durgam, a psychiatrist and senior vice president for late-stage clinical development and medical affairs at Intra-Cellular Therapies.

The most common adverse events with lumateperone were somnolence (24% vs. 10% on placebo) and dry mouth (6% vs. 2%).

Approval of lumateperone hit a snag last summer when the FDA canceled the Psychopharmacologic Drugs Advisory Committee meeting it previously had called for to review the new drug application for lumateperone. The agency said the meeting was canceled because of “new information regarding the application.”

At the time, Intra-Cellular Therapies noted that it had provided additional information to the FDA to meet agency requests. This information was related to nonclinical studies.

“The FDA canceled the advisory committee meeting to allow sufficient time to review this new and any forthcoming information as they continue” to review the new drug application for lumateperone, Intra-Cellular said a statement.

The company plans to launch Caplyta late in the first quarter of 2020.

[email protected]

Bruce Jancin and Kerry Dooley Young contributed to this report.

The Food and Drug Administration has approved lumateperone for the treatment of schizophrenia in adults.

Lumateperone, an atypical antipsychotic, will be marketed by Intra-Cellular Therapies as Caplyta, according to a Dec. 23 statement from the company.

Approval of the drug was based on two placebo-controlled trials. In the first, 335 patients with schizophrenia were randomized to two doses of lumateperone, an active comparator, or placebo. Those randomized to the approved 42-mg dose of lumateperone showed a statistically significant reduction in total score on the Positive and Negative Syndrome Scale (PANSS), compared with patients in the other groups. The median age in this study was 42 years; 17% of patients were female, 19% were white, and 78% were black.

In the second study, 450 patients diagnosed with schizophrenia were randomized in a double-blind fashion to one of two doses of lumateperone or placebo. Patients taking the approved dose showed a statistically significant reduction from baseline to day 28 in PANSS total score. In this study, patients’ median age was 44 years; 23% were female, 26% were white, and 66% were black.

Treatment with lumateperone appears to feature a more favorable cardiometabolic profile than that of other approved antipsychotic agents.

Patients treated with lumateperone for at least a year showed significant reductions in LDL cholesterol, total cholesterol, serum prolactin, and body weight, compared with baseline values recorded when participants were on various standard-of-care antipsychotics prior to switching, Suresh Durgam, MD, reported at the annual congress of the European College of Neuropsychopharmacology. Other cardiometabolic parameters, including fasting blood glucose, insulin, triglycerides, and HDL cholesterol, showed only negligible change over the course of study, according to Dr. Durgam, a psychiatrist and senior vice president for late-stage clinical development and medical affairs at Intra-Cellular Therapies.

The most common adverse events with lumateperone were somnolence (24% vs. 10% on placebo) and dry mouth (6% vs. 2%).

Approval of lumateperone hit a snag last summer when the FDA canceled the Psychopharmacologic Drugs Advisory Committee meeting it previously had called for to review the new drug application for lumateperone. The agency said the meeting was canceled because of “new information regarding the application.”

At the time, Intra-Cellular Therapies noted that it had provided additional information to the FDA to meet agency requests. This information was related to nonclinical studies.

“The FDA canceled the advisory committee meeting to allow sufficient time to review this new and any forthcoming information as they continue” to review the new drug application for lumateperone, Intra-Cellular said a statement.

The company plans to launch Caplyta late in the first quarter of 2020.

[email protected]

Bruce Jancin and Kerry Dooley Young contributed to this report.

BUSAN, SOUTH KOREA – With much misinformation online about diabetes, it is important to know which websites and other online portals offer trustworthy information for clinicians and patients with type 1 and type 2, says endocrinologist Irl B. Hirsch, MD, professor of medicine and diabetes treatment and teaching chair at the University of Washington, Seattle.

Speaking at the recent International Diabetes Federation Congress, Dr. Hirsch offered the international audience a list of sites he considers reliable and helpful, but with the caveat that “this is by no means a complete list, but these are some of my favorites.”

Session moderator David M. Maahs, MD, PhD, chief of pediatric endocrinology at Stanford (Calif.) University, said in an interview that it is now pointless to try to tell patients not to look things up online. “Everyone is going to go on the Internet, so point people in the right direction for reliable information,” he advised.

For general diabetes information, Dr. Hirsch said society websites are a good place for clinicians and patients to start. Among the best of these, he said, are:

• American Diabetes Association (ADA).
• Diabetes Australia.
• Diabetes UK.
• European Association for the Study of Diabetes (EASD).
• International Diabetes Federation (IDF).
• JDRF (type 1 diabetes).

Sites for type 1 diabetes

He pointed out in his talk that he was able to find many more reliable sites for type 1 diabetes than for type 2 diabetes. Among his top picks was the Children with Diabetes (CWD) website, which he said was “an outstanding site for type 1 diabetes for children, parents, grandparents, and also adults with type 1 diabetes.” Its content includes up-to-date information about all aspects of type 1 diabetes research, frequent polls of common questions, and discussion forums.

“It’s not just the United States. People from all over the world are looking at this site,” Dr. Hirsch noted.

For 2 decades, the CWD has sponsored the Friends for Life conference, which takes place in Orlando every July. The event is now attended by around 3,000 children and young adults with type 1 diabetes and their family members, he noted.

Dr. Maahs seconded Dr. Hirsch’s CWD recommendation. “They’ve continued to have a wonderful website, a great source of information. The conference is great. They’ll put you in touch with people in your area.”

Another good type 1 diabetes site for patients and families is that of the JDRF (formerly the Juvenile Diabetes Research Foundation), which provides “an outstanding review of type 1 diabetes research and social action,” Dr. Hirsch commented. In addition to the main site, there are also regional JDRF sites in Australia, the United Kingdom, and Canada.

Beyond Type 1 is part of a network that also includes Beyond Type 2 and Spanish-language sites for both Beyond Type 1 and Beyond Type 2. The sites feature news, stories, self-help, and resources.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) has a site for clinicians and families with type 1 diabetes, according to Dr. Hirsch. It provides information about events, resources, and guidelines. A recent article, for example, addresses fasting during Ramadan or young people with diabetes.

Dr. Maahs, who is secretary general of ISPAD and edited the organization’s 2018 Clinical Practice Consensus Guidelines, noted that all of the clinical guidelines and patient education materials are free on the site, as are conference presentations from the past 3 years. A lot of the material is also available in different languages, he noted.

He also pointed out that ISPAD’s recommendations for pediatric diabetes are mostly in line with that of the ADA, but they include far more information – 25 chapters versus just one ADA chapter. Also, in 2018, ISPAD lowered its A_1c target for children from 7.5% to 7.0%, which aligns with Scandinavian but not U.S. recommendations.

In addition to the type 1 diabetes sites that Dr. Hirsch listed, Dr. Maahs added the T1D Exchange online community site Glu, which he said was a good patient advocacy site.
 

Sites for type 2 diabetes

Dr. Hirsch recommended several sites for patients with type 2 diabetes, including:

• The Johns Hopkins Patient Guide to Diabetes, one of his favorite type 2 diabetes sites because of its “artistry, the graphics – you get it from just looking at the pictures. There’s a tech corner, videos, and patient stories. There’s just a lot here for patients.”
• Diabetes Sisters, specifically for women with diabetes.
• Diabetes Strong, which focuses on exercise.
• Wildly Fluctuating, with topics “from humor to serious stuff to miscellaneous musings on the diabetes news of the week by a type 2 diabetes patient/expert.”

Sites for clinicians

For clinicians, Dr. Hirsch said the following sites provide free and up-to-date information on the management of type 2 diabetes (some also include type 1 diabetes):

• ADA/EASD Standards of Care.
• Diabetes Canada 2018 Guidelines.
• American Association of Clinical Endocrinologists Type 2 Diabetes Management Algorithm.
• UK National Institute for Health and Care Excellence, which Dr. Hirsch called “extensive evidence-based guidelines. They really dig into the evidence as much, if not more, than most of the national standards of care around the world.”
• Clinical Diabetes, an ADA journal that provides “outstanding articles geared for nonspecialists free to clinicians online 6 months after publication.” It includes some primary data articles, but it is mostly review, he noted.

Regional sites

Dr. Hirsch included information about regional sites as well:

• Dr. Mohan’s Diabetes Specialties Centre, “a very good site for those living in India.”
• HealthDirect in Australia.
• Diabetes UK.

Dr. Hirsch is a consultant for Abbott Diabetes Care, Roche, and Bigfoot; conducts research for Medtronic; and is an editor on diabetes for UpToDate. Dr. Maahs has received research support from the National Institutes of Health, JDRF, National Science Foundation, and Leona M. and Harry B. Helmsley Charitable Trust and has consulted for Abbott, Helmsley, Sanofi, Novo Nordisk, Eli Lilly, and Insulet.
 

A version of this story originally appeared on Medscape.com.

BUSAN, SOUTH KOREA – With much misinformation online about diabetes, it is important to know which websites and other online portals offer trustworthy information for clinicians and patients with type 1 and type 2, says endocrinologist Irl B. Hirsch, MD, professor of medicine and diabetes treatment and teaching chair at the University of Washington, Seattle.

Speaking at the recent International Diabetes Federation Congress, Dr. Hirsch offered the international audience a list of sites he considers reliable and helpful, but with the caveat that “this is by no means a complete list, but these are some of my favorites.”

Session moderator David M. Maahs, MD, PhD, chief of pediatric endocrinology at Stanford (Calif.) University, said in an interview that it is now pointless to try to tell patients not to look things up online. “Everyone is going to go on the Internet, so point people in the right direction for reliable information,” he advised.

For general diabetes information, Dr. Hirsch said society websites are a good place for clinicians and patients to start. Among the best of these, he said, are:

• American Diabetes Association (ADA).
• Diabetes Australia.
• Diabetes UK.
• European Association for the Study of Diabetes (EASD).
• International Diabetes Federation (IDF).
• JDRF (type 1 diabetes).

Sites for type 1 diabetes

He pointed out in his talk that he was able to find many more reliable sites for type 1 diabetes than for type 2 diabetes. Among his top picks was the Children with Diabetes (CWD) website, which he said was “an outstanding site for type 1 diabetes for children, parents, grandparents, and also adults with type 1 diabetes.” Its content includes up-to-date information about all aspects of type 1 diabetes research, frequent polls of common questions, and discussion forums.

“It’s not just the United States. People from all over the world are looking at this site,” Dr. Hirsch noted.

For 2 decades, the CWD has sponsored the Friends for Life conference, which takes place in Orlando every July. The event is now attended by around 3,000 children and young adults with type 1 diabetes and their family members, he noted.

Dr. Maahs seconded Dr. Hirsch’s CWD recommendation. “They’ve continued to have a wonderful website, a great source of information. The conference is great. They’ll put you in touch with people in your area.”

Another good type 1 diabetes site for patients and families is that of the JDRF (formerly the Juvenile Diabetes Research Foundation), which provides “an outstanding review of type 1 diabetes research and social action,” Dr. Hirsch commented. In addition to the main site, there are also regional JDRF sites in Australia, the United Kingdom, and Canada.

Beyond Type 1 is part of a network that also includes Beyond Type 2 and Spanish-language sites for both Beyond Type 1 and Beyond Type 2. The sites feature news, stories, self-help, and resources.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) has a site for clinicians and families with type 1 diabetes, according to Dr. Hirsch. It provides information about events, resources, and guidelines. A recent article, for example, addresses fasting during Ramadan or young people with diabetes.

Dr. Maahs, who is secretary general of ISPAD and edited the organization’s 2018 Clinical Practice Consensus Guidelines, noted that all of the clinical guidelines and patient education materials are free on the site, as are conference presentations from the past 3 years. A lot of the material is also available in different languages, he noted.

He also pointed out that ISPAD’s recommendations for pediatric diabetes are mostly in line with that of the ADA, but they include far more information – 25 chapters versus just one ADA chapter. Also, in 2018, ISPAD lowered its A_1c target for children from 7.5% to 7.0%, which aligns with Scandinavian but not U.S. recommendations.

In addition to the type 1 diabetes sites that Dr. Hirsch listed, Dr. Maahs added the T1D Exchange online community site Glu, which he said was a good patient advocacy site.
 

Sites for type 2 diabetes

Dr. Hirsch recommended several sites for patients with type 2 diabetes, including:

• The Johns Hopkins Patient Guide to Diabetes, one of his favorite type 2 diabetes sites because of its “artistry, the graphics – you get it from just looking at the pictures. There’s a tech corner, videos, and patient stories. There’s just a lot here for patients.”
• Diabetes Sisters, specifically for women with diabetes.
• Diabetes Strong, which focuses on exercise.
• Wildly Fluctuating, with topics “from humor to serious stuff to miscellaneous musings on the diabetes news of the week by a type 2 diabetes patient/expert.”

Sites for clinicians

For clinicians, Dr. Hirsch said the following sites provide free and up-to-date information on the management of type 2 diabetes (some also include type 1 diabetes):

• ADA/EASD Standards of Care.
• Diabetes Canada 2018 Guidelines.
• American Association of Clinical Endocrinologists Type 2 Diabetes Management Algorithm.
• UK National Institute for Health and Care Excellence, which Dr. Hirsch called “extensive evidence-based guidelines. They really dig into the evidence as much, if not more, than most of the national standards of care around the world.”
• Clinical Diabetes, an ADA journal that provides “outstanding articles geared for nonspecialists free to clinicians online 6 months after publication.” It includes some primary data articles, but it is mostly review, he noted.

Regional sites

Dr. Hirsch included information about regional sites as well:

• Dr. Mohan’s Diabetes Specialties Centre, “a very good site for those living in India.”
• HealthDirect in Australia.
• Diabetes UK.

Dr. Hirsch is a consultant for Abbott Diabetes Care, Roche, and Bigfoot; conducts research for Medtronic; and is an editor on diabetes for UpToDate. Dr. Maahs has received research support from the National Institutes of Health, JDRF, National Science Foundation, and Leona M. and Harry B. Helmsley Charitable Trust and has consulted for Abbott, Helmsley, Sanofi, Novo Nordisk, Eli Lilly, and Insulet.
 

A version of this story originally appeared on Medscape.com.

BUSAN, SOUTH KOREA – With much misinformation online about diabetes, it is important to know which websites and other online portals offer trustworthy information for clinicians and patients with type 1 and type 2, says endocrinologist Irl B. Hirsch, MD, professor of medicine and diabetes treatment and teaching chair at the University of Washington, Seattle.

Speaking at the recent International Diabetes Federation Congress, Dr. Hirsch offered the international audience a list of sites he considers reliable and helpful, but with the caveat that “this is by no means a complete list, but these are some of my favorites.”

Session moderator David M. Maahs, MD, PhD, chief of pediatric endocrinology at Stanford (Calif.) University, said in an interview that it is now pointless to try to tell patients not to look things up online. “Everyone is going to go on the Internet, so point people in the right direction for reliable information,” he advised.

For general diabetes information, Dr. Hirsch said society websites are a good place for clinicians and patients to start. Among the best of these, he said, are:

• American Diabetes Association (ADA).
• Diabetes Australia.
• Diabetes UK.
• European Association for the Study of Diabetes (EASD).
• International Diabetes Federation (IDF).
• JDRF (type 1 diabetes).

Sites for type 1 diabetes

He pointed out in his talk that he was able to find many more reliable sites for type 1 diabetes than for type 2 diabetes. Among his top picks was the Children with Diabetes (CWD) website, which he said was “an outstanding site for type 1 diabetes for children, parents, grandparents, and also adults with type 1 diabetes.” Its content includes up-to-date information about all aspects of type 1 diabetes research, frequent polls of common questions, and discussion forums.

“It’s not just the United States. People from all over the world are looking at this site,” Dr. Hirsch noted.

For 2 decades, the CWD has sponsored the Friends for Life conference, which takes place in Orlando every July. The event is now attended by around 3,000 children and young adults with type 1 diabetes and their family members, he noted.

Dr. Maahs seconded Dr. Hirsch’s CWD recommendation. “They’ve continued to have a wonderful website, a great source of information. The conference is great. They’ll put you in touch with people in your area.”

Another good type 1 diabetes site for patients and families is that of the JDRF (formerly the Juvenile Diabetes Research Foundation), which provides “an outstanding review of type 1 diabetes research and social action,” Dr. Hirsch commented. In addition to the main site, there are also regional JDRF sites in Australia, the United Kingdom, and Canada.

Beyond Type 1 is part of a network that also includes Beyond Type 2 and Spanish-language sites for both Beyond Type 1 and Beyond Type 2. The sites feature news, stories, self-help, and resources.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) has a site for clinicians and families with type 1 diabetes, according to Dr. Hirsch. It provides information about events, resources, and guidelines. A recent article, for example, addresses fasting during Ramadan or young people with diabetes.

Dr. Maahs, who is secretary general of ISPAD and edited the organization’s 2018 Clinical Practice Consensus Guidelines, noted that all of the clinical guidelines and patient education materials are free on the site, as are conference presentations from the past 3 years. A lot of the material is also available in different languages, he noted.

He also pointed out that ISPAD’s recommendations for pediatric diabetes are mostly in line with that of the ADA, but they include far more information – 25 chapters versus just one ADA chapter. Also, in 2018, ISPAD lowered its A_1c target for children from 7.5% to 7.0%, which aligns with Scandinavian but not U.S. recommendations.

In addition to the type 1 diabetes sites that Dr. Hirsch listed, Dr. Maahs added the T1D Exchange online community site Glu, which he said was a good patient advocacy site.
 

Sites for type 2 diabetes

Dr. Hirsch recommended several sites for patients with type 2 diabetes, including:

• The Johns Hopkins Patient Guide to Diabetes, one of his favorite type 2 diabetes sites because of its “artistry, the graphics – you get it from just looking at the pictures. There’s a tech corner, videos, and patient stories. There’s just a lot here for patients.”
• Diabetes Sisters, specifically for women with diabetes.
• Diabetes Strong, which focuses on exercise.
• Wildly Fluctuating, with topics “from humor to serious stuff to miscellaneous musings on the diabetes news of the week by a type 2 diabetes patient/expert.”

Sites for clinicians

For clinicians, Dr. Hirsch said the following sites provide free and up-to-date information on the management of type 2 diabetes (some also include type 1 diabetes):

• ADA/EASD Standards of Care.
• Diabetes Canada 2018 Guidelines.
• American Association of Clinical Endocrinologists Type 2 Diabetes Management Algorithm.
• UK National Institute for Health and Care Excellence, which Dr. Hirsch called “extensive evidence-based guidelines. They really dig into the evidence as much, if not more, than most of the national standards of care around the world.”
• Clinical Diabetes, an ADA journal that provides “outstanding articles geared for nonspecialists free to clinicians online 6 months after publication.” It includes some primary data articles, but it is mostly review, he noted.

Regional sites

Dr. Hirsch included information about regional sites as well:

• Dr. Mohan’s Diabetes Specialties Centre, “a very good site for those living in India.”
• HealthDirect in Australia.
• Diabetes UK.

Dr. Hirsch is a consultant for Abbott Diabetes Care, Roche, and Bigfoot; conducts research for Medtronic; and is an editor on diabetes for UpToDate. Dr. Maahs has received research support from the National Institutes of Health, JDRF, National Science Foundation, and Leona M. and Harry B. Helmsley Charitable Trust and has consulted for Abbott, Helmsley, Sanofi, Novo Nordisk, Eli Lilly, and Insulet.
 

A version of this story originally appeared on Medscape.com.

Editor's note: This article was originally published in the January/February 2003 issue of Clinician News. It placed first in the journal's Most Unusual Patient Contest.

Late one morning, a woman and her 13-year-old daughter came into our office. “Mrs. Smith” reported that “Lisa” had a retained tampon. Lisa looked scared as her mother did all of the talking.

One of the male doctors saw Lisa first. After about 10 minutes, he emerged from the examination room looking perplexed. He said he wasn’t sure what was going on. He asked me to go in and try to get Lisa to allow a more thorough pelvic examination.

My exam of Lisa proved only slightly easier. I was able to visualize something curved and firm that sounded like plastic when touched with the ring forceps. I could pull the object as far as the vaginal introitus, but it would always slide back. “This is no tampon,” I repeated several times. Each time I pulled down, Lisa became more agitated. After several tries, I gave Lisa a rest and left the room to consult with a doctor.

The doctor suggested a trip to same-day surgery for evaluation under anesthesia but decided to give it one more try before heading for the operating room.

Continue to: Together, we entered the exam room...

Together, we entered the exam room. “Well, we’ve had some true confessions,” Mrs. Smith said dryly. “Lisa has a Christmas bell in her vagina—obviously the work of a curious 13-year-old!”

The doctor and I were taken by surprise, but we proceeded with the challenge of the day. Thinking we were dealing with a standard Christmas bell, we attempted to break the suction of the bell on Lisa’s cervix. This proved to be more difficult than we anticipated. After getting a closer look at the bell, we realized that it was a “jingle” bell rather than a standard bell shape.

The crosshair opening of the jingle bell had slipped over Lisa’s cervix. The cervix had become edematous and necrotic. The doctor gave one final pull, and the bell—with cervical tissue inside—flew out.

We needed pliers to open the bell so we could send a tissue sample to the pathology department for evaluation. Lisa received high-dose antibiotics and after several follow-up visits, she was declared healed.

This patient encounter, which also falls under the categories of unbelievable, unconventional, and amazing, was definitely unforgettable to me.

Editor's note: This article was originally published in the January/February 2003 issue of Clinician News. It placed first in the journal's Most Unusual Patient Contest.

Late one morning, a woman and her 13-year-old daughter came into our office. “Mrs. Smith” reported that “Lisa” had a retained tampon. Lisa looked scared as her mother did all of the talking.

One of the male doctors saw Lisa first. After about 10 minutes, he emerged from the examination room looking perplexed. He said he wasn’t sure what was going on. He asked me to go in and try to get Lisa to allow a more thorough pelvic examination.

My exam of Lisa proved only slightly easier. I was able to visualize something curved and firm that sounded like plastic when touched with the ring forceps. I could pull the object as far as the vaginal introitus, but it would always slide back. “This is no tampon,” I repeated several times. Each time I pulled down, Lisa became more agitated. After several tries, I gave Lisa a rest and left the room to consult with a doctor.

The doctor suggested a trip to same-day surgery for evaluation under anesthesia but decided to give it one more try before heading for the operating room.

Continue to: Together, we entered the exam room...

Together, we entered the exam room. “Well, we’ve had some true confessions,” Mrs. Smith said dryly. “Lisa has a Christmas bell in her vagina—obviously the work of a curious 13-year-old!”

The doctor and I were taken by surprise, but we proceeded with the challenge of the day. Thinking we were dealing with a standard Christmas bell, we attempted to break the suction of the bell on Lisa’s cervix. This proved to be more difficult than we anticipated. After getting a closer look at the bell, we realized that it was a “jingle” bell rather than a standard bell shape.

The crosshair opening of the jingle bell had slipped over Lisa’s cervix. The cervix had become edematous and necrotic. The doctor gave one final pull, and the bell—with cervical tissue inside—flew out.

We needed pliers to open the bell so we could send a tissue sample to the pathology department for evaluation. Lisa received high-dose antibiotics and after several follow-up visits, she was declared healed.

This patient encounter, which also falls under the categories of unbelievable, unconventional, and amazing, was definitely unforgettable to me.

Editor's note: This article was originally published in the January/February 2003 issue of Clinician News. It placed first in the journal's Most Unusual Patient Contest.

Late one morning, a woman and her 13-year-old daughter came into our office. “Mrs. Smith” reported that “Lisa” had a retained tampon. Lisa looked scared as her mother did all of the talking.

One of the male doctors saw Lisa first. After about 10 minutes, he emerged from the examination room looking perplexed. He said he wasn’t sure what was going on. He asked me to go in and try to get Lisa to allow a more thorough pelvic examination.

My exam of Lisa proved only slightly easier. I was able to visualize something curved and firm that sounded like plastic when touched with the ring forceps. I could pull the object as far as the vaginal introitus, but it would always slide back. “This is no tampon,” I repeated several times. Each time I pulled down, Lisa became more agitated. After several tries, I gave Lisa a rest and left the room to consult with a doctor.

The doctor suggested a trip to same-day surgery for evaluation under anesthesia but decided to give it one more try before heading for the operating room.

Continue to: Together, we entered the exam room...

Together, we entered the exam room. “Well, we’ve had some true confessions,” Mrs. Smith said dryly. “Lisa has a Christmas bell in her vagina—obviously the work of a curious 13-year-old!”

The doctor and I were taken by surprise, but we proceeded with the challenge of the day. Thinking we were dealing with a standard Christmas bell, we attempted to break the suction of the bell on Lisa’s cervix. This proved to be more difficult than we anticipated. After getting a closer look at the bell, we realized that it was a “jingle” bell rather than a standard bell shape.

The crosshair opening of the jingle bell had slipped over Lisa’s cervix. The cervix had become edematous and necrotic. The doctor gave one final pull, and the bell—with cervical tissue inside—flew out.

We needed pliers to open the bell so we could send a tissue sample to the pathology department for evaluation. Lisa received high-dose antibiotics and after several follow-up visits, she was declared healed.

This patient encounter, which also falls under the categories of unbelievable, unconventional, and amazing, was definitely unforgettable to me.

This year’s Specialty Match Day was highlighted by the addition of four new programs and 13 new fellowship positions for future rheumatologists.

For the 2020 appointment year, there were 249 fellowships in rheumatology available, up from 236 in the previous year. It continues a trend of an increasing number of fellowship slots. There were 221 slots available in the 2018 appointment year.

There were 242 slots filled in the 2020 appointment year, up from 233 in the previous year and 218 from two appointment years ago.

“The overall message from the match this year in rheumatology is that it really was a very good, very successful match,” Beth Jonas, MD, chair of the American College of Rheumatology’s Committee on Training and Workforce Issues, said in an interview. “Rheumatology continues to be extremely strong in terms of its ability to attract excellent physicians to the subspecialty, so we are really very, very happy about that.”

She also applauded the addition of the four new programs and 13 new fellowship slots.

“We’ve been working very hard to try and figure out ways to increase slots,” said Dr. Jonas, a professor at the University of North Carolina, Chapel Hill. She noted that while more needs to be done to address future workforce needs, even the small increases “are meaningful. There is the knowledge out there that there is a workforce shortage in rheumatology. There certainly are a lot of people who would like to become rheumatologists. There is a little bit of a bottleneck here at the level of training slots to get interested and qualified applicants into the match and matched with programs, so we’ve had some marginal increases there.”

[email protected]

SOURCE: National Resident Matching Program.

This year’s Specialty Match Day was highlighted by the addition of four new programs and 13 new fellowship positions for future rheumatologists.

For the 2020 appointment year, there were 249 fellowships in rheumatology available, up from 236 in the previous year. It continues a trend of an increasing number of fellowship slots. There were 221 slots available in the 2018 appointment year.

There were 242 slots filled in the 2020 appointment year, up from 233 in the previous year and 218 from two appointment years ago.

“The overall message from the match this year in rheumatology is that it really was a very good, very successful match,” Beth Jonas, MD, chair of the American College of Rheumatology’s Committee on Training and Workforce Issues, said in an interview. “Rheumatology continues to be extremely strong in terms of its ability to attract excellent physicians to the subspecialty, so we are really very, very happy about that.”

She also applauded the addition of the four new programs and 13 new fellowship slots.

“We’ve been working very hard to try and figure out ways to increase slots,” said Dr. Jonas, a professor at the University of North Carolina, Chapel Hill. She noted that while more needs to be done to address future workforce needs, even the small increases “are meaningful. There is the knowledge out there that there is a workforce shortage in rheumatology. There certainly are a lot of people who would like to become rheumatologists. There is a little bit of a bottleneck here at the level of training slots to get interested and qualified applicants into the match and matched with programs, so we’ve had some marginal increases there.”

[email protected]

SOURCE: National Resident Matching Program.

This year’s Specialty Match Day was highlighted by the addition of four new programs and 13 new fellowship positions for future rheumatologists.

For the 2020 appointment year, there were 249 fellowships in rheumatology available, up from 236 in the previous year. It continues a trend of an increasing number of fellowship slots. There were 221 slots available in the 2018 appointment year.

There were 242 slots filled in the 2020 appointment year, up from 233 in the previous year and 218 from two appointment years ago.

“The overall message from the match this year in rheumatology is that it really was a very good, very successful match,” Beth Jonas, MD, chair of the American College of Rheumatology’s Committee on Training and Workforce Issues, said in an interview. “Rheumatology continues to be extremely strong in terms of its ability to attract excellent physicians to the subspecialty, so we are really very, very happy about that.”

She also applauded the addition of the four new programs and 13 new fellowship slots.

“We’ve been working very hard to try and figure out ways to increase slots,” said Dr. Jonas, a professor at the University of North Carolina, Chapel Hill. She noted that while more needs to be done to address future workforce needs, even the small increases “are meaningful. There is the knowledge out there that there is a workforce shortage in rheumatology. There certainly are a lot of people who would like to become rheumatologists. There is a little bit of a bottleneck here at the level of training slots to get interested and qualified applicants into the match and matched with programs, so we’ve had some marginal increases there.”

[email protected]

SOURCE: National Resident Matching Program.

LAS VEGAS – Surgical repair of pelvic organ prolapse often may seem like an uncomplicated procedure. But many factors play roles into decisions, and surgeons around the world vary widely in how they handle the operations, Mark D. Walters, MD, told colleagues at the Pelvic Anatomy and Gynecologic Surgery Symposium.

“These prolapse repairs seem relatively simple at first, but they’re not simple at all,” he said. “Experts can have completely different and sometimes almost opposite opinions” on how to perform pelvic organ prolapse repairs.
 

Questions to ask prior to surgery

It’s important to first answer a number of questions, said Dr. Walters, professor and vice-chair of gynecology at the Cleveland Clinic. “When you see a patient like this, you may not realize how many decisions you’re making.”

These questions include:

• Is the patient sexually active or planning to be?
• Has she had a hysterectomy, and or is one necessary? If so, how should it be done? What does the patient think about a hysterectomy?
• Should the prolapse procedure be performed vaginally, open, laparoscopically, or robotically?
• Is adding a graft advisable? What kind?
• Should there be a sling to prevent stress urinary incontinence?”

Dr. Walters talked to colleagues from several nations and learned about these variations in surgical techniques.

Chinese surgeons use a variety of techniques with transvaginal mesh (TVM). Their use is more common in more populated cities because of the effect of medical education; native tissue procedures are more common in less-populated regions that are considered “backward.”

TVM with hysteropexy (“apical sling”) also is common in Latin America, while Middle Eastern surgeons have little training in female pelvic medicine and reconstructive surgery.

In Europe, France embraces mesh surgery and laparoscopy, while the United Kingdom has “completely abandoned” mesh surgery, and the Netherlands rarely uses it in favor of vaginal procedures.

In the United States, he said, TVM is “discouraged” while a variety of other procedures are used.

What procedures should surgeons embrace? There are many topics of debate, Dr. Walters said, including type of transvaginal repair (native tissue or mesh-augmented or sacrocolpopexy?), repair of “defects” in the vagina (even if they’re nonsymptomatic?) and the removal of the uterus (yes or no?).

Dr. Walters pointed to several explanations for this variation, including lack of high-quality research, confirmation bias, economic conflicts – surgeons are in the business of surgery, after all – and lack of insight into what women prefer.
 

Consider patient choice

In a survey, Dr. Walters polled women in their 50s with this question: “How much do you value your uterus?” Three women, he said, had widely varied opinions on a scale of 1-10, with one at 10 and another at 0.

“A doctor doesn’t know this and doesn’t have a way to ask, and the doctor has [his/her] own opinion about the value of the uterus,” he said. “Shouldn’t we know what patients think?”
 

How to measure success

He offered these tips about measuring success:

• Focus on symptomatic cure more than clinical cure.
• Remember that perfect anatomic support isn’t linked to health-related quality of life, and some loss of anatomic support is normal.
• Understand that commonly used definitions of anatomic success often aren’t clinically relevant.

Dr. Walters’ disclosures: royalties (Elsevier, UpToDate), website/lecturer (International Academy of Pelvic Surgery), and website editor (Foundation for Female Health Awareness).

This meeting was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

LAS VEGAS – Surgical repair of pelvic organ prolapse often may seem like an uncomplicated procedure. But many factors play roles into decisions, and surgeons around the world vary widely in how they handle the operations, Mark D. Walters, MD, told colleagues at the Pelvic Anatomy and Gynecologic Surgery Symposium.

“These prolapse repairs seem relatively simple at first, but they’re not simple at all,” he said. “Experts can have completely different and sometimes almost opposite opinions” on how to perform pelvic organ prolapse repairs.
 

Questions to ask prior to surgery

It’s important to first answer a number of questions, said Dr. Walters, professor and vice-chair of gynecology at the Cleveland Clinic. “When you see a patient like this, you may not realize how many decisions you’re making.”

These questions include:

• Is the patient sexually active or planning to be?
• Has she had a hysterectomy, and or is one necessary? If so, how should it be done? What does the patient think about a hysterectomy?
• Should the prolapse procedure be performed vaginally, open, laparoscopically, or robotically?
• Is adding a graft advisable? What kind?
• Should there be a sling to prevent stress urinary incontinence?”

Dr. Walters talked to colleagues from several nations and learned about these variations in surgical techniques.

Chinese surgeons use a variety of techniques with transvaginal mesh (TVM). Their use is more common in more populated cities because of the effect of medical education; native tissue procedures are more common in less-populated regions that are considered “backward.”

TVM with hysteropexy (“apical sling”) also is common in Latin America, while Middle Eastern surgeons have little training in female pelvic medicine and reconstructive surgery.

In Europe, France embraces mesh surgery and laparoscopy, while the United Kingdom has “completely abandoned” mesh surgery, and the Netherlands rarely uses it in favor of vaginal procedures.

In the United States, he said, TVM is “discouraged” while a variety of other procedures are used.

What procedures should surgeons embrace? There are many topics of debate, Dr. Walters said, including type of transvaginal repair (native tissue or mesh-augmented or sacrocolpopexy?), repair of “defects” in the vagina (even if they’re nonsymptomatic?) and the removal of the uterus (yes or no?).

Dr. Walters pointed to several explanations for this variation, including lack of high-quality research, confirmation bias, economic conflicts – surgeons are in the business of surgery, after all – and lack of insight into what women prefer.
 

Consider patient choice

In a survey, Dr. Walters polled women in their 50s with this question: “How much do you value your uterus?” Three women, he said, had widely varied opinions on a scale of 1-10, with one at 10 and another at 0.

“A doctor doesn’t know this and doesn’t have a way to ask, and the doctor has [his/her] own opinion about the value of the uterus,” he said. “Shouldn’t we know what patients think?”
 

How to measure success

He offered these tips about measuring success:

• Focus on symptomatic cure more than clinical cure.
• Remember that perfect anatomic support isn’t linked to health-related quality of life, and some loss of anatomic support is normal.
• Understand that commonly used definitions of anatomic success often aren’t clinically relevant.

Dr. Walters’ disclosures: royalties (Elsevier, UpToDate), website/lecturer (International Academy of Pelvic Surgery), and website editor (Foundation for Female Health Awareness).

This meeting was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

LAS VEGAS – Surgical repair of pelvic organ prolapse often may seem like an uncomplicated procedure. But many factors play roles into decisions, and surgeons around the world vary widely in how they handle the operations, Mark D. Walters, MD, told colleagues at the Pelvic Anatomy and Gynecologic Surgery Symposium.

“These prolapse repairs seem relatively simple at first, but they’re not simple at all,” he said. “Experts can have completely different and sometimes almost opposite opinions” on how to perform pelvic organ prolapse repairs.
 

Questions to ask prior to surgery

It’s important to first answer a number of questions, said Dr. Walters, professor and vice-chair of gynecology at the Cleveland Clinic. “When you see a patient like this, you may not realize how many decisions you’re making.”

These questions include:

• Is the patient sexually active or planning to be?
• Has she had a hysterectomy, and or is one necessary? If so, how should it be done? What does the patient think about a hysterectomy?
• Should the prolapse procedure be performed vaginally, open, laparoscopically, or robotically?
• Is adding a graft advisable? What kind?
• Should there be a sling to prevent stress urinary incontinence?”

Dr. Walters talked to colleagues from several nations and learned about these variations in surgical techniques.

Chinese surgeons use a variety of techniques with transvaginal mesh (TVM). Their use is more common in more populated cities because of the effect of medical education; native tissue procedures are more common in less-populated regions that are considered “backward.”

TVM with hysteropexy (“apical sling”) also is common in Latin America, while Middle Eastern surgeons have little training in female pelvic medicine and reconstructive surgery.

In Europe, France embraces mesh surgery and laparoscopy, while the United Kingdom has “completely abandoned” mesh surgery, and the Netherlands rarely uses it in favor of vaginal procedures.

In the United States, he said, TVM is “discouraged” while a variety of other procedures are used.

What procedures should surgeons embrace? There are many topics of debate, Dr. Walters said, including type of transvaginal repair (native tissue or mesh-augmented or sacrocolpopexy?), repair of “defects” in the vagina (even if they’re nonsymptomatic?) and the removal of the uterus (yes or no?).

Dr. Walters pointed to several explanations for this variation, including lack of high-quality research, confirmation bias, economic conflicts – surgeons are in the business of surgery, after all – and lack of insight into what women prefer.
 

Consider patient choice

In a survey, Dr. Walters polled women in their 50s with this question: “How much do you value your uterus?” Three women, he said, had widely varied opinions on a scale of 1-10, with one at 10 and another at 0.

“A doctor doesn’t know this and doesn’t have a way to ask, and the doctor has [his/her] own opinion about the value of the uterus,” he said. “Shouldn’t we know what patients think?”
 

How to measure success

He offered these tips about measuring success:

• Focus on symptomatic cure more than clinical cure.
• Remember that perfect anatomic support isn’t linked to health-related quality of life, and some loss of anatomic support is normal.
• Understand that commonly used definitions of anatomic success often aren’t clinically relevant.

Dr. Walters’ disclosures: royalties (Elsevier, UpToDate), website/lecturer (International Academy of Pelvic Surgery), and website editor (Foundation for Female Health Awareness).

This meeting was jointly provided by Global Academy for Medical Education and the University of Cincinnati. Global Academy and this news organization are owned by the same company.

WASHINGTON – Insulin is the preferred agent for type 2 diabetes in pregnant women, yet about a third of pregnancies still have an adverse outcome, according Kim Boggess, MD, who spoke at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“We are not where we need to be,” said Dr. Boggess, who is leading a trial that brings metformin, the first-line agent for type 2 diabetes outside of pregnancy, back into the picture for pregnant women – as an add-on to insulin.

It is an interesting twist, because pregnant women taking metformin for preexisting type 2 or gestational diabetes have been shown in some studies to require supplemental insulin, more than occasionally, to achieve target glycemic control.

This was the case in a small, randomized, controlled trial at Dr. Boggess’ institution, the University of North Carolina at Chapel Hill, in which 43% of pregnant women with type 2 diabetes who were assigned to metformin required supplemental insulin (Am J Perinatol. 2013;30[6]:483-90). The study also found, however, that women treated with metformin had significantly fewer episodes of hypoglycemia, compared with women using insulin (0% vs. 36%, respectively) and fewer reports of glucose values less than 60 mg/dL (7.1% vs. 50%).

“I don’t consider this [need for supplemental insulin] ‘metformin failure,’ because studies that use metformin as monotherapy and that [show some patients] ultimately requiring insulin support ... also show that these women need less insulin,” she said. “What’s the risk of insulin alone? Hypoglycemia. So using less insulin could be a good thing.”

Other research suggests there may be less maternal weight gain, less neonatal hypoglycemia, fewer neonatal complications, and improved maternal glycemic control in patients treated with metformin, alone or with add-on insulin, than with insulin alone. “We’re starting to get a sense in the literature that, at least in the [pregnant] population with type 2 diabetes, there may be a role for metformin,” said Dr. Boggess, professor and program director for maternal-fetal medicine at the university.

* This article was updated 1/2/2020.

WASHINGTON – Insulin is the preferred agent for type 2 diabetes in pregnant women, yet about a third of pregnancies still have an adverse outcome, according Kim Boggess, MD, who spoke at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“We are not where we need to be,” said Dr. Boggess, who is leading a trial that brings metformin, the first-line agent for type 2 diabetes outside of pregnancy, back into the picture for pregnant women – as an add-on to insulin.

It is an interesting twist, because pregnant women taking metformin for preexisting type 2 or gestational diabetes have been shown in some studies to require supplemental insulin, more than occasionally, to achieve target glycemic control.

This was the case in a small, randomized, controlled trial at Dr. Boggess’ institution, the University of North Carolina at Chapel Hill, in which 43% of pregnant women with type 2 diabetes who were assigned to metformin required supplemental insulin (Am J Perinatol. 2013;30[6]:483-90). The study also found, however, that women treated with metformin had significantly fewer episodes of hypoglycemia, compared with women using insulin (0% vs. 36%, respectively) and fewer reports of glucose values less than 60 mg/dL (7.1% vs. 50%).

“I don’t consider this [need for supplemental insulin] ‘metformin failure,’ because studies that use metformin as monotherapy and that [show some patients] ultimately requiring insulin support ... also show that these women need less insulin,” she said. “What’s the risk of insulin alone? Hypoglycemia. So using less insulin could be a good thing.”

Other research suggests there may be less maternal weight gain, less neonatal hypoglycemia, fewer neonatal complications, and improved maternal glycemic control in patients treated with metformin, alone or with add-on insulin, than with insulin alone. “We’re starting to get a sense in the literature that, at least in the [pregnant] population with type 2 diabetes, there may be a role for metformin,” said Dr. Boggess, professor and program director for maternal-fetal medicine at the university.

* This article was updated 1/2/2020.

WASHINGTON – Insulin is the preferred agent for type 2 diabetes in pregnant women, yet about a third of pregnancies still have an adverse outcome, according Kim Boggess, MD, who spoke at the biennial meeting of the Diabetes in Pregnancy Study Group of North America.

“We are not where we need to be,” said Dr. Boggess, who is leading a trial that brings metformin, the first-line agent for type 2 diabetes outside of pregnancy, back into the picture for pregnant women – as an add-on to insulin.

It is an interesting twist, because pregnant women taking metformin for preexisting type 2 or gestational diabetes have been shown in some studies to require supplemental insulin, more than occasionally, to achieve target glycemic control.

This was the case in a small, randomized, controlled trial at Dr. Boggess’ institution, the University of North Carolina at Chapel Hill, in which 43% of pregnant women with type 2 diabetes who were assigned to metformin required supplemental insulin (Am J Perinatol. 2013;30[6]:483-90). The study also found, however, that women treated with metformin had significantly fewer episodes of hypoglycemia, compared with women using insulin (0% vs. 36%, respectively) and fewer reports of glucose values less than 60 mg/dL (7.1% vs. 50%).

“I don’t consider this [need for supplemental insulin] ‘metformin failure,’ because studies that use metformin as monotherapy and that [show some patients] ultimately requiring insulin support ... also show that these women need less insulin,” she said. “What’s the risk of insulin alone? Hypoglycemia. So using less insulin could be a good thing.”

Other research suggests there may be less maternal weight gain, less neonatal hypoglycemia, fewer neonatal complications, and improved maternal glycemic control in patients treated with metformin, alone or with add-on insulin, than with insulin alone. “We’re starting to get a sense in the literature that, at least in the [pregnant] population with type 2 diabetes, there may be a role for metformin,” said Dr. Boggess, professor and program director for maternal-fetal medicine at the university.

* This article was updated 1/2/2020.

Vitamin E acetate was found in fluid from the lungs of 94% of patients with electronic cigarette, or vaping, product use–associated lung injury, data from a convenience sample of 51 patients indicate. The findings were published in the New England Journal of Medicine.

Cases of electronic cigarette, or vaping, product use–associated lung injury (EVALI) were reported to the Centers for Disease Control and Prevention starting in early 2019, and numbers rose throughout the year, “which suggests new or increased exposure to one or more toxicants from the use of e-cigarette products,” wrote Benjamin C. Blount, PhD, of the National Center for Environmental Health at the CDC, and colleagues.

To further investigate potential toxins in patients with EVALI, the researchers examined bronchoalveolar-lavage (BAL) fluid from 51 EVALI patients and 99 healthy controls.

After the researchers used isotope dilution mass spectrometry on the samples, 48 of the 51 patients (94%) showed vitamin E acetate in their BAL samples. No other potential toxins – including plant oils, medium-chain triglyceride oil, petroleum distillates, and diluent terpenes – were identified. The samples of one patient each showed coconut oil and limonene.

A total of 47 of 51 patients for whom complete laboratory data were available either reported vaping tetrahydrocannabinol products within 90 days of becoming ill, or showed tetrahydrocannabinol or its metabolites in their BAL fluid. In addition, 30 of 47 patients showed nicotine or nicotine metabolites in their BAL fluid.

The average age of the patients was 23 years, 69% were male. Overall, 25 were confirmed EVALI cases and 26 were probable cases, and probable cases included the three patients who showed no vitamin E acetate.

The safety of inhaling vitamin E acetate, which is a common ingredient in dietary supplements and skin care creams, has not been well studied. It could contribute to lung injury when heated in e-cigarette products by splitting the acetate to create the reactive compound and potential lung irritant ketene, the researchers said.

The study findings were limited by several factors including the possibility that vitamin E acetate is a marker for exposure to other toxicants, a lack of data on the impact of heating vitamin e acetate, and the inability to assess the timing of the vitamin E acetate exposure compared to BAL sample collection, the researchers noted.

However, the results suggest that vitamin E acetate may play a role in EVALI because of the high detection rate in patients from across the United States, the biologically possible potential for lung injury from vitamin e acetate, and the timing of the rise of EVALI and the use of vitamin E acetate in vaping products, they concluded.

The research was supported by the National Cancer Institute, the FDA Center for Tobacco Products, and The Ohio State University Pelotonia intramural research program. The authors had no financial conflicts to disclose.

SOURCE: Blount BC et al. N Engl J Med. 2019 Dec 20. doi: 10.1056/NEJMoa1916433.

Vitamin E acetate was found in fluid from the lungs of 94% of patients with electronic cigarette, or vaping, product use–associated lung injury, data from a convenience sample of 51 patients indicate. The findings were published in the New England Journal of Medicine.

Cases of electronic cigarette, or vaping, product use–associated lung injury (EVALI) were reported to the Centers for Disease Control and Prevention starting in early 2019, and numbers rose throughout the year, “which suggests new or increased exposure to one or more toxicants from the use of e-cigarette products,” wrote Benjamin C. Blount, PhD, of the National Center for Environmental Health at the CDC, and colleagues.

To further investigate potential toxins in patients with EVALI, the researchers examined bronchoalveolar-lavage (BAL) fluid from 51 EVALI patients and 99 healthy controls.

After the researchers used isotope dilution mass spectrometry on the samples, 48 of the 51 patients (94%) showed vitamin E acetate in their BAL samples. No other potential toxins – including plant oils, medium-chain triglyceride oil, petroleum distillates, and diluent terpenes – were identified. The samples of one patient each showed coconut oil and limonene.

A total of 47 of 51 patients for whom complete laboratory data were available either reported vaping tetrahydrocannabinol products within 90 days of becoming ill, or showed tetrahydrocannabinol or its metabolites in their BAL fluid. In addition, 30 of 47 patients showed nicotine or nicotine metabolites in their BAL fluid.

The average age of the patients was 23 years, 69% were male. Overall, 25 were confirmed EVALI cases and 26 were probable cases, and probable cases included the three patients who showed no vitamin E acetate.

The safety of inhaling vitamin E acetate, which is a common ingredient in dietary supplements and skin care creams, has not been well studied. It could contribute to lung injury when heated in e-cigarette products by splitting the acetate to create the reactive compound and potential lung irritant ketene, the researchers said.

The study findings were limited by several factors including the possibility that vitamin E acetate is a marker for exposure to other toxicants, a lack of data on the impact of heating vitamin e acetate, and the inability to assess the timing of the vitamin E acetate exposure compared to BAL sample collection, the researchers noted.

However, the results suggest that vitamin E acetate may play a role in EVALI because of the high detection rate in patients from across the United States, the biologically possible potential for lung injury from vitamin e acetate, and the timing of the rise of EVALI and the use of vitamin E acetate in vaping products, they concluded.

The research was supported by the National Cancer Institute, the FDA Center for Tobacco Products, and The Ohio State University Pelotonia intramural research program. The authors had no financial conflicts to disclose.

SOURCE: Blount BC et al. N Engl J Med. 2019 Dec 20. doi: 10.1056/NEJMoa1916433.

Vitamin E acetate was found in fluid from the lungs of 94% of patients with electronic cigarette, or vaping, product use–associated lung injury, data from a convenience sample of 51 patients indicate. The findings were published in the New England Journal of Medicine.

Cases of electronic cigarette, or vaping, product use–associated lung injury (EVALI) were reported to the Centers for Disease Control and Prevention starting in early 2019, and numbers rose throughout the year, “which suggests new or increased exposure to one or more toxicants from the use of e-cigarette products,” wrote Benjamin C. Blount, PhD, of the National Center for Environmental Health at the CDC, and colleagues.

To further investigate potential toxins in patients with EVALI, the researchers examined bronchoalveolar-lavage (BAL) fluid from 51 EVALI patients and 99 healthy controls.

After the researchers used isotope dilution mass spectrometry on the samples, 48 of the 51 patients (94%) showed vitamin E acetate in their BAL samples. No other potential toxins – including plant oils, medium-chain triglyceride oil, petroleum distillates, and diluent terpenes – were identified. The samples of one patient each showed coconut oil and limonene.

A total of 47 of 51 patients for whom complete laboratory data were available either reported vaping tetrahydrocannabinol products within 90 days of becoming ill, or showed tetrahydrocannabinol or its metabolites in their BAL fluid. In addition, 30 of 47 patients showed nicotine or nicotine metabolites in their BAL fluid.

The average age of the patients was 23 years, 69% were male. Overall, 25 were confirmed EVALI cases and 26 were probable cases, and probable cases included the three patients who showed no vitamin E acetate.

The safety of inhaling vitamin E acetate, which is a common ingredient in dietary supplements and skin care creams, has not been well studied. It could contribute to lung injury when heated in e-cigarette products by splitting the acetate to create the reactive compound and potential lung irritant ketene, the researchers said.

The study findings were limited by several factors including the possibility that vitamin E acetate is a marker for exposure to other toxicants, a lack of data on the impact of heating vitamin e acetate, and the inability to assess the timing of the vitamin E acetate exposure compared to BAL sample collection, the researchers noted.

However, the results suggest that vitamin E acetate may play a role in EVALI because of the high detection rate in patients from across the United States, the biologically possible potential for lung injury from vitamin e acetate, and the timing of the rise of EVALI and the use of vitamin E acetate in vaping products, they concluded.

The research was supported by the National Cancer Institute, the FDA Center for Tobacco Products, and The Ohio State University Pelotonia intramural research program. The authors had no financial conflicts to disclose.

SOURCE: Blount BC et al. N Engl J Med. 2019 Dec 20. doi: 10.1056/NEJMoa1916433.

A Food and Drug Administration advisory panel unanimously recommended approval of teprotumumab solution for intravenous use for the treatment of active thyroid eye disease (TED).

TED is a rare autoimmune disease that causes the eyes to bulge (proptosis) and can lead to blindness. It is also known as thyroid-associated ophthalmopathy, Graves ophthalmopathy, and Graves orbitopathy. Current treatment is aimed at relief of symptoms and includes corticosteroids and orbital decompression.

“TED can affect patients both physically and emotionally, limiting their ability to perform everyday activities like driving, working, reading, sleeping, and participating in social activities,” Jeff Todd, president and chief executive officer, Prevent Blindness, said in a news release.

“As an organization dedicated to helping patients with vision impairment and those who are at significant risk, we are extremely encouraged by today’s vote and hopeful this will change the future of TED treatment by giving patients an option that has been shown to improve the painful and vision-threatening aspects of the disease,” Mr. Todd said.

Teprotumumab was granted fast-track status in April 2015 and breakthrough therapy designation in July 2016. It received orphan drug designation on June 19, 2019. If approved, it would be the first approved treatment for this indication.

All 12 members of the Dermatologic and Ophthalmic Drugs Advisory Committee of the FDA voted to recommend approval of teprotumumab.

“It’s clearly a pleasure to participate in seeing a drug being designed and moving forward in a clinical trial for a disease that really has not been treatable for us in the past,” said voting committee member Timothy Murray, MD, MBA, of the Bascom Palmer Eye Institute, Miami.
 

Efficacy demonstrated

The FDA advisory committee considered data from two randomized, double-masked, placebo-controlled, parallel-group studies that were similar in design and that demonstrated efficacy.

The studies included a total of 171 patients, fewer than 90 of whom were treated with teprotumumab, the agency explained in a briefing document. “This is a considerably smaller database than the common safety database of greater than 300 patients treated with a course of therapy,” it observed.

The study required that patients have proptosis but did not require that they have “progressive forward motion of the globe,” it noted.

The primary objective – a reduction in proptosis of 2 or more mm – was met in 82% of patients who received teprotumumab, compared with 16% of those who received placebo.

Review study No. 1 (TED01RV) was a phase 2 study, and review study No. 2 (OPTIC) was a phase 3 study. Both trials included a 24-week treatment period during which participants received teprotumumab or placebo intravenously every 3 weeks for a total of eight doses. Patients in both studies underwent a follow-up period during which they received no further treatment.

Some patients experienced a reduction in proptosis as early as 6 weeks after they received the first infusion. In an extension of TED01RV, that reduction extended for at least 4 weeks after the last infusion. For about 60% of responders, no relapse had occurred by week 72. The extension of OPTIC and an open-label treatment period for those with no response to placebo or teprotumumab are ongoing.

“I welcome the addition of this drug to our armamentarium to treat this horrible, horrible disease,” said temporary voting committee member John F. Stamler, MD, PhD, clinical instructor, ophthalmology and visual sciences, University of Iowa, Iowa City.
 

Adverse events

Teprotumumab inhibits the insulinlike growth factor–1 receptor, which can interfere with the body’s ability to regulate glucose, particularly in patients with diabetes. In the study, some patients with diabetes required additional insulin for glycemic control.

In three study participants whose baseline fasting blood glucose levels were normal, blood glucose levels were found to be elevated at one or more visits during the treatment period. None had a history of diabetes mellitus, but for two, baseline hemoglobin A_1c levels were elevated.

Five or more patients reported loss of hearing (hypoacusis), and others reported tinnitus. One of them experienced a spontaneous return of hearing the day after the hypoacusis developed, whereas for others, hearing did not return until after teprotumumab treatment was completed. The mechanism of action for hearing loss is unclear.

Panel members felt the potential for hearing loss is important and that patients should receive some type of monitoring, but they did not all agree on when that testing should occur or who should be responsible for getting it done.

“It strikes me that, if this drug were approved, there would be centers that would be interested in undertaking independent studies of hearing loss in treated patients, and that that could be done outside the sponsor’s responsibility and probably would be of interest to independent investigators,” noted committee chairperson James Chodosh, MD, MPH, of Massachusetts Eye and Ear and Harvard Medical School, Boston.
 

Benefits outweigh risks

More than one-third of patients (36%) experienced gastrointestinal complaints such as nausea and diarrhea (12% each) and abdominal pain (5%). None of the cases caused any patient to discontinue the study drug.

The overall incidence of muscle spasms was more than three times higher in the teprotumumab group (32%) than in the placebo group (9.5%).

One patient stopped taking teprotumumab after being hospitalized for Escherichia coli sepsis and dehydration, and another participant stopped after experiencing an episode of inflammatory bowel disease. It is not clear whether there is a causal association between teprotumumab and inflammatory bowel disease.

No study participants died.

Panel members expressed concern about safety in the longer term or in patients who receive multiple courses of teprotumumab, but they felt the potential benefits from teprotumumab outweigh the risks. The committee also wanted more information about the effects of teprotumumab with respect to glucose control, hearing loss, and other outcomes that are very important to patients, such as alopecia.

The panel favored including diarrhea in the list of adverse events in the label and felt that there should be a warning about inflammatory bowel disease.

“We’re finally going to be able to get a lot of people some help,” concluded voting committee member Sidney Gicheru, MD, LaserCare Eye Center, Irving, Texas.
 

A version of this story originally appeared on Medscape.com.

A Food and Drug Administration advisory panel unanimously recommended approval of teprotumumab solution for intravenous use for the treatment of active thyroid eye disease (TED).

TED is a rare autoimmune disease that causes the eyes to bulge (proptosis) and can lead to blindness. It is also known as thyroid-associated ophthalmopathy, Graves ophthalmopathy, and Graves orbitopathy. Current treatment is aimed at relief of symptoms and includes corticosteroids and orbital decompression.

“TED can affect patients both physically and emotionally, limiting their ability to perform everyday activities like driving, working, reading, sleeping, and participating in social activities,” Jeff Todd, president and chief executive officer, Prevent Blindness, said in a news release.

“As an organization dedicated to helping patients with vision impairment and those who are at significant risk, we are extremely encouraged by today’s vote and hopeful this will change the future of TED treatment by giving patients an option that has been shown to improve the painful and vision-threatening aspects of the disease,” Mr. Todd said.

Teprotumumab was granted fast-track status in April 2015 and breakthrough therapy designation in July 2016. It received orphan drug designation on June 19, 2019. If approved, it would be the first approved treatment for this indication.

All 12 members of the Dermatologic and Ophthalmic Drugs Advisory Committee of the FDA voted to recommend approval of teprotumumab.

“It’s clearly a pleasure to participate in seeing a drug being designed and moving forward in a clinical trial for a disease that really has not been treatable for us in the past,” said voting committee member Timothy Murray, MD, MBA, of the Bascom Palmer Eye Institute, Miami.
 

Efficacy demonstrated

The FDA advisory committee considered data from two randomized, double-masked, placebo-controlled, parallel-group studies that were similar in design and that demonstrated efficacy.

The studies included a total of 171 patients, fewer than 90 of whom were treated with teprotumumab, the agency explained in a briefing document. “This is a considerably smaller database than the common safety database of greater than 300 patients treated with a course of therapy,” it observed.

The study required that patients have proptosis but did not require that they have “progressive forward motion of the globe,” it noted.

The primary objective – a reduction in proptosis of 2 or more mm – was met in 82% of patients who received teprotumumab, compared with 16% of those who received placebo.

Review study No. 1 (TED01RV) was a phase 2 study, and review study No. 2 (OPTIC) was a phase 3 study. Both trials included a 24-week treatment period during which participants received teprotumumab or placebo intravenously every 3 weeks for a total of eight doses. Patients in both studies underwent a follow-up period during which they received no further treatment.

Some patients experienced a reduction in proptosis as early as 6 weeks after they received the first infusion. In an extension of TED01RV, that reduction extended for at least 4 weeks after the last infusion. For about 60% of responders, no relapse had occurred by week 72. The extension of OPTIC and an open-label treatment period for those with no response to placebo or teprotumumab are ongoing.

“I welcome the addition of this drug to our armamentarium to treat this horrible, horrible disease,” said temporary voting committee member John F. Stamler, MD, PhD, clinical instructor, ophthalmology and visual sciences, University of Iowa, Iowa City.
 

Adverse events

Teprotumumab inhibits the insulinlike growth factor–1 receptor, which can interfere with the body’s ability to regulate glucose, particularly in patients with diabetes. In the study, some patients with diabetes required additional insulin for glycemic control.

In three study participants whose baseline fasting blood glucose levels were normal, blood glucose levels were found to be elevated at one or more visits during the treatment period. None had a history of diabetes mellitus, but for two, baseline hemoglobin A_1c levels were elevated.

Five or more patients reported loss of hearing (hypoacusis), and others reported tinnitus. One of them experienced a spontaneous return of hearing the day after the hypoacusis developed, whereas for others, hearing did not return until after teprotumumab treatment was completed. The mechanism of action for hearing loss is unclear.

Panel members felt the potential for hearing loss is important and that patients should receive some type of monitoring, but they did not all agree on when that testing should occur or who should be responsible for getting it done.

“It strikes me that, if this drug were approved, there would be centers that would be interested in undertaking independent studies of hearing loss in treated patients, and that that could be done outside the sponsor’s responsibility and probably would be of interest to independent investigators,” noted committee chairperson James Chodosh, MD, MPH, of Massachusetts Eye and Ear and Harvard Medical School, Boston.
 

Benefits outweigh risks

More than one-third of patients (36%) experienced gastrointestinal complaints such as nausea and diarrhea (12% each) and abdominal pain (5%). None of the cases caused any patient to discontinue the study drug.

The overall incidence of muscle spasms was more than three times higher in the teprotumumab group (32%) than in the placebo group (9.5%).

One patient stopped taking teprotumumab after being hospitalized for Escherichia coli sepsis and dehydration, and another participant stopped after experiencing an episode of inflammatory bowel disease. It is not clear whether there is a causal association between teprotumumab and inflammatory bowel disease.

No study participants died.

Panel members expressed concern about safety in the longer term or in patients who receive multiple courses of teprotumumab, but they felt the potential benefits from teprotumumab outweigh the risks. The committee also wanted more information about the effects of teprotumumab with respect to glucose control, hearing loss, and other outcomes that are very important to patients, such as alopecia.

The panel favored including diarrhea in the list of adverse events in the label and felt that there should be a warning about inflammatory bowel disease.

“We’re finally going to be able to get a lot of people some help,” concluded voting committee member Sidney Gicheru, MD, LaserCare Eye Center, Irving, Texas.
 

A version of this story originally appeared on Medscape.com.

A Food and Drug Administration advisory panel unanimously recommended approval of teprotumumab solution for intravenous use for the treatment of active thyroid eye disease (TED).

TED is a rare autoimmune disease that causes the eyes to bulge (proptosis) and can lead to blindness. It is also known as thyroid-associated ophthalmopathy, Graves ophthalmopathy, and Graves orbitopathy. Current treatment is aimed at relief of symptoms and includes corticosteroids and orbital decompression.

“TED can affect patients both physically and emotionally, limiting their ability to perform everyday activities like driving, working, reading, sleeping, and participating in social activities,” Jeff Todd, president and chief executive officer, Prevent Blindness, said in a news release.

“As an organization dedicated to helping patients with vision impairment and those who are at significant risk, we are extremely encouraged by today’s vote and hopeful this will change the future of TED treatment by giving patients an option that has been shown to improve the painful and vision-threatening aspects of the disease,” Mr. Todd said.

Teprotumumab was granted fast-track status in April 2015 and breakthrough therapy designation in July 2016. It received orphan drug designation on June 19, 2019. If approved, it would be the first approved treatment for this indication.

All 12 members of the Dermatologic and Ophthalmic Drugs Advisory Committee of the FDA voted to recommend approval of teprotumumab.

“It’s clearly a pleasure to participate in seeing a drug being designed and moving forward in a clinical trial for a disease that really has not been treatable for us in the past,” said voting committee member Timothy Murray, MD, MBA, of the Bascom Palmer Eye Institute, Miami.
 

Efficacy demonstrated

The FDA advisory committee considered data from two randomized, double-masked, placebo-controlled, parallel-group studies that were similar in design and that demonstrated efficacy.

The studies included a total of 171 patients, fewer than 90 of whom were treated with teprotumumab, the agency explained in a briefing document. “This is a considerably smaller database than the common safety database of greater than 300 patients treated with a course of therapy,” it observed.

The study required that patients have proptosis but did not require that they have “progressive forward motion of the globe,” it noted.

The primary objective – a reduction in proptosis of 2 or more mm – was met in 82% of patients who received teprotumumab, compared with 16% of those who received placebo.

Review study No. 1 (TED01RV) was a phase 2 study, and review study No. 2 (OPTIC) was a phase 3 study. Both trials included a 24-week treatment period during which participants received teprotumumab or placebo intravenously every 3 weeks for a total of eight doses. Patients in both studies underwent a follow-up period during which they received no further treatment.

Some patients experienced a reduction in proptosis as early as 6 weeks after they received the first infusion. In an extension of TED01RV, that reduction extended for at least 4 weeks after the last infusion. For about 60% of responders, no relapse had occurred by week 72. The extension of OPTIC and an open-label treatment period for those with no response to placebo or teprotumumab are ongoing.

“I welcome the addition of this drug to our armamentarium to treat this horrible, horrible disease,” said temporary voting committee member John F. Stamler, MD, PhD, clinical instructor, ophthalmology and visual sciences, University of Iowa, Iowa City.
 

Adverse events

Teprotumumab inhibits the insulinlike growth factor–1 receptor, which can interfere with the body’s ability to regulate glucose, particularly in patients with diabetes. In the study, some patients with diabetes required additional insulin for glycemic control.

In three study participants whose baseline fasting blood glucose levels were normal, blood glucose levels were found to be elevated at one or more visits during the treatment period. None had a history of diabetes mellitus, but for two, baseline hemoglobin A_1c levels were elevated.

Five or more patients reported loss of hearing (hypoacusis), and others reported tinnitus. One of them experienced a spontaneous return of hearing the day after the hypoacusis developed, whereas for others, hearing did not return until after teprotumumab treatment was completed. The mechanism of action for hearing loss is unclear.

Panel members felt the potential for hearing loss is important and that patients should receive some type of monitoring, but they did not all agree on when that testing should occur or who should be responsible for getting it done.

“It strikes me that, if this drug were approved, there would be centers that would be interested in undertaking independent studies of hearing loss in treated patients, and that that could be done outside the sponsor’s responsibility and probably would be of interest to independent investigators,” noted committee chairperson James Chodosh, MD, MPH, of Massachusetts Eye and Ear and Harvard Medical School, Boston.
 

Benefits outweigh risks

More than one-third of patients (36%) experienced gastrointestinal complaints such as nausea and diarrhea (12% each) and abdominal pain (5%). None of the cases caused any patient to discontinue the study drug.

The overall incidence of muscle spasms was more than three times higher in the teprotumumab group (32%) than in the placebo group (9.5%).

One patient stopped taking teprotumumab after being hospitalized for Escherichia coli sepsis and dehydration, and another participant stopped after experiencing an episode of inflammatory bowel disease. It is not clear whether there is a causal association between teprotumumab and inflammatory bowel disease.

No study participants died.

Panel members expressed concern about safety in the longer term or in patients who receive multiple courses of teprotumumab, but they felt the potential benefits from teprotumumab outweigh the risks. The committee also wanted more information about the effects of teprotumumab with respect to glucose control, hearing loss, and other outcomes that are very important to patients, such as alopecia.

The panel favored including diarrhea in the list of adverse events in the label and felt that there should be a warning about inflammatory bowel disease.

“We’re finally going to be able to get a lot of people some help,” concluded voting committee member Sidney Gicheru, MD, LaserCare Eye Center, Irving, Texas.
 

A version of this story originally appeared on Medscape.com.