This week, a revelation that coronary artery bypass grafting instead of percutaneous is safer as time goes by, a new index stretches the prognostic power of cardiac CT, a weight-loss drug cuts new-onset diabetes, and a controversial diet score is validated.

Subscribe to Cardiocast wherever you get your podcasts:
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This week, a revelation that coronary artery bypass grafting instead of percutaneous is safer as time goes by, a new index stretches the prognostic power of cardiac CT, a weight-loss drug cuts new-onset diabetes, and a controversial diet score is validated.

Subscribe to Cardiocast wherever you get your podcasts:
Amazon Alexa
Apple Podcasts

This week, a revelation that coronary artery bypass grafting instead of percutaneous is safer as time goes by, a new index stretches the prognostic power of cardiac CT, a weight-loss drug cuts new-onset diabetes, and a controversial diet score is validated.

Subscribe to Cardiocast wherever you get your podcasts:
Amazon Alexa
Apple Podcasts

A wise person once said, “Research is a marathon and not a sprint.” Grant writing is the training for the marathon, and it requires discipline and fortitude to succeed. We are junior faculty members with mentored career development awards who are transitioning to independence. Below, we provide for our junior faculty colleagues some tips that have helped us train for our marathon in research.

Identify great mentors

We all understand that outstanding mentorship is critical to success. With that said, we often struggle to understand what a good mentor is. In regard to grant writing, you need someone who is willing to use red ink. While positive reinforcement may be good for your self-esteem, your mentor needs to be critical so that you can learn how to present the best possible product. In return, you must be an invested mentee who is respectful of the mentor’s time, is prepared for meetings, and responds appropriately to feedback.

Attend workshops

Your home institution and professional societies hold outstanding workshops that provide didactic lessons on both the logistics and mechanics of grant writing and allow you to network with like-minded peers, potential mentors, and staff from the funding organization. One excellent example is the American Gastroenterological Association/American Association for the Study of Liver Diseases (AGA/AASLD) Academic Skills workshop.

Decide on a grant mechanism

There are many different grants available through the government, industry, foundations, and your institution. Each grantor may have a variety of mechanisms from pilot awards to larger multiprovider and institution grants. Deciding which grants to apply for can be more of an art than it is a science. Research the opportunities available to you and develop a long-term plan with your mentors.

Start early and have a plan

An effective grant application is prepared in steps, and every step takes longer than anticipated. About 6 months prior to the deadline, read the instructions and consider using something like a Gantt chart to identify all required sections, special requirements (font, spacing, page limits), and anticipated time of completion. Then, structure a reasonable timeline – and stick to it! Remember to allow ample time for all sections, including the career development plan and research environment. Your institution will probably request the documents early, anywhere from 1 to 2 weeks prior to the deadline so that it can be circulated for institutional signatures. Steady progress wins most races.

Specific aims

There is no grant without a great idea, but not all great ideas are funded. So, the first step is to polish your idea, which must be clearly described on the Specific Aims page, which is a one-page summary that lays the framework for the rest of the grant. For the primary reviewers, it should entice them to read the proposal. For others on the review panel, it may be the only section of your grant that they read. Make sure it is clear and concise. If possible, construct a visually pleasing and easy-to-follow figure that encapsulates your proposal.

Circulate

Ideally, every section of the grant will be circulated but it is critical to have others review the Specific Aims at the very least. Ask not only your mentors and those in the field to critique but also those outside of your area and even your friends and unsuspecting family members; they may not know (or care) about the content but should be able to follow the flow and identify grammatical errors. Remember that everyone is busy, so give ample time for people to review the documents.

Read other proposals

Practice makes perfect. So you can either apply for many grants and make the mistakes yourself or read and review as many proposals as you can to learn from your colleagues’ successes and mistakes. Many institutions, mentors, and colleagues will provide copies of prior applications if you ask. Make sure you know which were successful and try to understand why the others were not successful.

When reading the aims and research strategy, pay close attention to how significance and innovation are detailed. Also, some things like the research environment, which is especially important for career development grants, may be directly applicable to your grant.
 

Help the reviewer

In general, reviewing grants is a voluntary undertaking. Imagine the reviewer reading your grant at a home filled with screaming children or, alternatively, flying in cramped quarters. Neither situation is stress-free, so put yourself in those positions and decide what you can do to make the reviewer’s job easier.

Use figures and tables to summarize the text, and consider coming back to the figure from your Specific Aims to refer to the specific parts of the proposal. You can decrease reviewer fatigue by using line breaks and fonts to break up sections and highlight important details. This will also be helpful to the reviewers on the panel who were not assigned to your grant and possibly first seeing it during the session.
 

Learn from rejection

You are either a savant or have not applied for enough grants if you have not received a rejection letter. Often, reviewers provide you with constructive comments, which (after a session of crying in the corner in a fetal position), you can use to improve your grant. Resubmission works!

Apply widely

Identify different possible grants, and work with your mentors on a strategy that allows you to make your idea versatile and package it for various funding mechanisms. Once you have a grant, you can tailor it to other grants as needed. However, remember that quantity does not replace quality, so many poor grants that are not funded will not replace one good one that is funded.

There are multiple approaches to training for the marathon of research, so these tips are not a comprehensive list or mandatory commandments. They have, however, proven invaluable to our mentors and us. Our institutions, societies and government agencies have identified the decline of young scientists and physician-scientists as a major leak in the research pipeline, so there are excellent funding mechanisms that are available to you. Good luck!

We would like to acknowledge Jennifer Weiss, MD, and Sumera Rizvi, MD, for their constructive comments.
 

Dr. Beyder is with the enteric neuroscience program, a consultant for the department of gastroenterology and hepatology, and an assistant professor of biomedical engineering and physiology at the Mayo Clinic School of Medicine, Rochester, Minn.; Dr. Twyman-Saint Victor is an assistant professor of medicine in the division of gastroenterology at the University of Pennsylvania, Philadelphia.

A wise person once said, “Research is a marathon and not a sprint.” Grant writing is the training for the marathon, and it requires discipline and fortitude to succeed. We are junior faculty members with mentored career development awards who are transitioning to independence. Below, we provide for our junior faculty colleagues some tips that have helped us train for our marathon in research.

Identify great mentors

We all understand that outstanding mentorship is critical to success. With that said, we often struggle to understand what a good mentor is. In regard to grant writing, you need someone who is willing to use red ink. While positive reinforcement may be good for your self-esteem, your mentor needs to be critical so that you can learn how to present the best possible product. In return, you must be an invested mentee who is respectful of the mentor’s time, is prepared for meetings, and responds appropriately to feedback.

Attend workshops

Your home institution and professional societies hold outstanding workshops that provide didactic lessons on both the logistics and mechanics of grant writing and allow you to network with like-minded peers, potential mentors, and staff from the funding organization. One excellent example is the American Gastroenterological Association/American Association for the Study of Liver Diseases (AGA/AASLD) Academic Skills workshop.

Decide on a grant mechanism

There are many different grants available through the government, industry, foundations, and your institution. Each grantor may have a variety of mechanisms from pilot awards to larger multiprovider and institution grants. Deciding which grants to apply for can be more of an art than it is a science. Research the opportunities available to you and develop a long-term plan with your mentors.

Start early and have a plan

An effective grant application is prepared in steps, and every step takes longer than anticipated. About 6 months prior to the deadline, read the instructions and consider using something like a Gantt chart to identify all required sections, special requirements (font, spacing, page limits), and anticipated time of completion. Then, structure a reasonable timeline – and stick to it! Remember to allow ample time for all sections, including the career development plan and research environment. Your institution will probably request the documents early, anywhere from 1 to 2 weeks prior to the deadline so that it can be circulated for institutional signatures. Steady progress wins most races.

Specific aims

There is no grant without a great idea, but not all great ideas are funded. So, the first step is to polish your idea, which must be clearly described on the Specific Aims page, which is a one-page summary that lays the framework for the rest of the grant. For the primary reviewers, it should entice them to read the proposal. For others on the review panel, it may be the only section of your grant that they read. Make sure it is clear and concise. If possible, construct a visually pleasing and easy-to-follow figure that encapsulates your proposal.

Circulate

Ideally, every section of the grant will be circulated but it is critical to have others review the Specific Aims at the very least. Ask not only your mentors and those in the field to critique but also those outside of your area and even your friends and unsuspecting family members; they may not know (or care) about the content but should be able to follow the flow and identify grammatical errors. Remember that everyone is busy, so give ample time for people to review the documents.

Read other proposals

Practice makes perfect. So you can either apply for many grants and make the mistakes yourself or read and review as many proposals as you can to learn from your colleagues’ successes and mistakes. Many institutions, mentors, and colleagues will provide copies of prior applications if you ask. Make sure you know which were successful and try to understand why the others were not successful.

When reading the aims and research strategy, pay close attention to how significance and innovation are detailed. Also, some things like the research environment, which is especially important for career development grants, may be directly applicable to your grant.
 

Help the reviewer

In general, reviewing grants is a voluntary undertaking. Imagine the reviewer reading your grant at a home filled with screaming children or, alternatively, flying in cramped quarters. Neither situation is stress-free, so put yourself in those positions and decide what you can do to make the reviewer’s job easier.

Use figures and tables to summarize the text, and consider coming back to the figure from your Specific Aims to refer to the specific parts of the proposal. You can decrease reviewer fatigue by using line breaks and fonts to break up sections and highlight important details. This will also be helpful to the reviewers on the panel who were not assigned to your grant and possibly first seeing it during the session.
 

Learn from rejection

You are either a savant or have not applied for enough grants if you have not received a rejection letter. Often, reviewers provide you with constructive comments, which (after a session of crying in the corner in a fetal position), you can use to improve your grant. Resubmission works!

Apply widely

Identify different possible grants, and work with your mentors on a strategy that allows you to make your idea versatile and package it for various funding mechanisms. Once you have a grant, you can tailor it to other grants as needed. However, remember that quantity does not replace quality, so many poor grants that are not funded will not replace one good one that is funded.

There are multiple approaches to training for the marathon of research, so these tips are not a comprehensive list or mandatory commandments. They have, however, proven invaluable to our mentors and us. Our institutions, societies and government agencies have identified the decline of young scientists and physician-scientists as a major leak in the research pipeline, so there are excellent funding mechanisms that are available to you. Good luck!

We would like to acknowledge Jennifer Weiss, MD, and Sumera Rizvi, MD, for their constructive comments.
 

Dr. Beyder is with the enteric neuroscience program, a consultant for the department of gastroenterology and hepatology, and an assistant professor of biomedical engineering and physiology at the Mayo Clinic School of Medicine, Rochester, Minn.; Dr. Twyman-Saint Victor is an assistant professor of medicine in the division of gastroenterology at the University of Pennsylvania, Philadelphia.

A wise person once said, “Research is a marathon and not a sprint.” Grant writing is the training for the marathon, and it requires discipline and fortitude to succeed. We are junior faculty members with mentored career development awards who are transitioning to independence. Below, we provide for our junior faculty colleagues some tips that have helped us train for our marathon in research.

Identify great mentors

We all understand that outstanding mentorship is critical to success. With that said, we often struggle to understand what a good mentor is. In regard to grant writing, you need someone who is willing to use red ink. While positive reinforcement may be good for your self-esteem, your mentor needs to be critical so that you can learn how to present the best possible product. In return, you must be an invested mentee who is respectful of the mentor’s time, is prepared for meetings, and responds appropriately to feedback.

Attend workshops

Your home institution and professional societies hold outstanding workshops that provide didactic lessons on both the logistics and mechanics of grant writing and allow you to network with like-minded peers, potential mentors, and staff from the funding organization. One excellent example is the American Gastroenterological Association/American Association for the Study of Liver Diseases (AGA/AASLD) Academic Skills workshop.

Decide on a grant mechanism

There are many different grants available through the government, industry, foundations, and your institution. Each grantor may have a variety of mechanisms from pilot awards to larger multiprovider and institution grants. Deciding which grants to apply for can be more of an art than it is a science. Research the opportunities available to you and develop a long-term plan with your mentors.

Start early and have a plan

An effective grant application is prepared in steps, and every step takes longer than anticipated. About 6 months prior to the deadline, read the instructions and consider using something like a Gantt chart to identify all required sections, special requirements (font, spacing, page limits), and anticipated time of completion. Then, structure a reasonable timeline – and stick to it! Remember to allow ample time for all sections, including the career development plan and research environment. Your institution will probably request the documents early, anywhere from 1 to 2 weeks prior to the deadline so that it can be circulated for institutional signatures. Steady progress wins most races.

Specific aims

There is no grant without a great idea, but not all great ideas are funded. So, the first step is to polish your idea, which must be clearly described on the Specific Aims page, which is a one-page summary that lays the framework for the rest of the grant. For the primary reviewers, it should entice them to read the proposal. For others on the review panel, it may be the only section of your grant that they read. Make sure it is clear and concise. If possible, construct a visually pleasing and easy-to-follow figure that encapsulates your proposal.

Circulate

Ideally, every section of the grant will be circulated but it is critical to have others review the Specific Aims at the very least. Ask not only your mentors and those in the field to critique but also those outside of your area and even your friends and unsuspecting family members; they may not know (or care) about the content but should be able to follow the flow and identify grammatical errors. Remember that everyone is busy, so give ample time for people to review the documents.

Read other proposals

Practice makes perfect. So you can either apply for many grants and make the mistakes yourself or read and review as many proposals as you can to learn from your colleagues’ successes and mistakes. Many institutions, mentors, and colleagues will provide copies of prior applications if you ask. Make sure you know which were successful and try to understand why the others were not successful.

When reading the aims and research strategy, pay close attention to how significance and innovation are detailed. Also, some things like the research environment, which is especially important for career development grants, may be directly applicable to your grant.
 

Help the reviewer

In general, reviewing grants is a voluntary undertaking. Imagine the reviewer reading your grant at a home filled with screaming children or, alternatively, flying in cramped quarters. Neither situation is stress-free, so put yourself in those positions and decide what you can do to make the reviewer’s job easier.

Use figures and tables to summarize the text, and consider coming back to the figure from your Specific Aims to refer to the specific parts of the proposal. You can decrease reviewer fatigue by using line breaks and fonts to break up sections and highlight important details. This will also be helpful to the reviewers on the panel who were not assigned to your grant and possibly first seeing it during the session.
 

Learn from rejection

You are either a savant or have not applied for enough grants if you have not received a rejection letter. Often, reviewers provide you with constructive comments, which (after a session of crying in the corner in a fetal position), you can use to improve your grant. Resubmission works!

Apply widely

Identify different possible grants, and work with your mentors on a strategy that allows you to make your idea versatile and package it for various funding mechanisms. Once you have a grant, you can tailor it to other grants as needed. However, remember that quantity does not replace quality, so many poor grants that are not funded will not replace one good one that is funded.

There are multiple approaches to training for the marathon of research, so these tips are not a comprehensive list or mandatory commandments. They have, however, proven invaluable to our mentors and us. Our institutions, societies and government agencies have identified the decline of young scientists and physician-scientists as a major leak in the research pipeline, so there are excellent funding mechanisms that are available to you. Good luck!

We would like to acknowledge Jennifer Weiss, MD, and Sumera Rizvi, MD, for their constructive comments.
 

Dr. Beyder is with the enteric neuroscience program, a consultant for the department of gastroenterology and hepatology, and an assistant professor of biomedical engineering and physiology at the Mayo Clinic School of Medicine, Rochester, Minn.; Dr. Twyman-Saint Victor is an assistant professor of medicine in the division of gastroenterology at the University of Pennsylvania, Philadelphia.

PARIS – Bronchiectasis responds to mepolizumab if the clinical profile includes eosinophilia, according to a small case series of patients presented as a late-breaking study at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge Newws

“The message is that it is important to think of all of the etiologies and treatable traits in patients with bronchiectasis, and do not forget eosinophilia, because this can be treated,” reported Jessica Rademacher, MD, of the Clinic for Pulmonology at Hannover (Germany) Medical School.

Mepolizumab is a monoclonal antibody that targets interleukin-5, an important signaling protein for eosinophil recruitment, and is approved for use in asthma with eosinophilia. Larger, controlled trials are needed to confirm its efficacy in bronchiectasis, but the clinical improvements after 6 months of treatment in a series of 12 patients at Dr. Rademacher’s center were impressive.

Bronchiectasis patients were selected for treatment with mepolizumab if they had been poorly controlled on conventional therapies and they had an eosinophil count of greater than 300 cells/mm³. Of 328 patients with bronchiectasis that are being followed at Dr. Rademacher’s center, 7% met these criteria. Dr. Rademacher presented data on 12 who had been followed for at least 6 months.

In these patients, the median eosinophil count fell from a median baseline of 1,000 cells/mm³ to 100 cells/mm³ at 6 months (P = .0012). The median annualized rate of exacerbations fell from three per year to one per year, and the median Modified Medical Research Council Dyspnea Scale score fell from 2 to 0 (P = .004).

“There was a steroid-sparing effect in all seven patients who were taking oral corticosteroids at baseline. Five stopped oral steroids completely,” Dr. Rademacher reported.

A visual analog scale ranging from 1 to 10 with higher scores representing improvement showed patient-rated quality of life improved from 4 to 6.5 (P = .01). Dr. Rademacher emphasized this outcome because “improved quality of life is really what we are trying to achieve.”

Mepolizumab was well tolerated. In one patient who developed pneumonia, mepolizumab was discontinued, but it was restarted when the infection resolved, because the pneumonia was not considered mepolizumab related.

Although Dr. Rademacher acknowledged the possibility that at least some of the patients in this case series had overlapping asthma, she emphasized that they were selected from a referral population that had a comprehensive workup and that this overlap has been rarely reported.

There is evidence that anti–interleukin-5 therapies such as mepolizumab are effective in respiratory diseases when eosinophilia is present, according to Dr. Rademacher. For example, she cited reports of clinical improvement in chronic obstructive pulmonary disease and granulomatosis with polyangiitis patients with high eosinophil counts. In bronchiectasis, which has many causes, it may be particularly important to select relevant targets.

“There is an important variability in the presentation of bronchiectasis. Not all these patients have reduced lung function,” she said. Rather, the most significant symptoms for a patient may be sputum or cough. She suggested that the goals are to identify underlying causes of symptoms and which may be treatable.

According to these data, eosinophilia may be one of the treatable causes in a small but significant proportion of patients with bronchiectasis. A trial of mepolizumab may be reasonable in patients inadequately controlled on inhaled anti-inflammatory drugs. “If they do not profit from this therapy, then stop,” she added.

Dr. Rademacher acknowledged that data from this small case series are “not enough to say that [mepolizumab] is an option for these patients,” but she believes the consistency of benefit in this small series will encourage the trials needed to confirm that this approach is safe and effective.

Dr. Rademacher reported no disclosures relevant to the report.

PARIS – Bronchiectasis responds to mepolizumab if the clinical profile includes eosinophilia, according to a small case series of patients presented as a late-breaking study at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge Newws

“The message is that it is important to think of all of the etiologies and treatable traits in patients with bronchiectasis, and do not forget eosinophilia, because this can be treated,” reported Jessica Rademacher, MD, of the Clinic for Pulmonology at Hannover (Germany) Medical School.

Mepolizumab is a monoclonal antibody that targets interleukin-5, an important signaling protein for eosinophil recruitment, and is approved for use in asthma with eosinophilia. Larger, controlled trials are needed to confirm its efficacy in bronchiectasis, but the clinical improvements after 6 months of treatment in a series of 12 patients at Dr. Rademacher’s center were impressive.

Bronchiectasis patients were selected for treatment with mepolizumab if they had been poorly controlled on conventional therapies and they had an eosinophil count of greater than 300 cells/mm³. Of 328 patients with bronchiectasis that are being followed at Dr. Rademacher’s center, 7% met these criteria. Dr. Rademacher presented data on 12 who had been followed for at least 6 months.

In these patients, the median eosinophil count fell from a median baseline of 1,000 cells/mm³ to 100 cells/mm³ at 6 months (P = .0012). The median annualized rate of exacerbations fell from three per year to one per year, and the median Modified Medical Research Council Dyspnea Scale score fell from 2 to 0 (P = .004).

“There was a steroid-sparing effect in all seven patients who were taking oral corticosteroids at baseline. Five stopped oral steroids completely,” Dr. Rademacher reported.

A visual analog scale ranging from 1 to 10 with higher scores representing improvement showed patient-rated quality of life improved from 4 to 6.5 (P = .01). Dr. Rademacher emphasized this outcome because “improved quality of life is really what we are trying to achieve.”

Mepolizumab was well tolerated. In one patient who developed pneumonia, mepolizumab was discontinued, but it was restarted when the infection resolved, because the pneumonia was not considered mepolizumab related.

Although Dr. Rademacher acknowledged the possibility that at least some of the patients in this case series had overlapping asthma, she emphasized that they were selected from a referral population that had a comprehensive workup and that this overlap has been rarely reported.

There is evidence that anti–interleukin-5 therapies such as mepolizumab are effective in respiratory diseases when eosinophilia is present, according to Dr. Rademacher. For example, she cited reports of clinical improvement in chronic obstructive pulmonary disease and granulomatosis with polyangiitis patients with high eosinophil counts. In bronchiectasis, which has many causes, it may be particularly important to select relevant targets.

“There is an important variability in the presentation of bronchiectasis. Not all these patients have reduced lung function,” she said. Rather, the most significant symptoms for a patient may be sputum or cough. She suggested that the goals are to identify underlying causes of symptoms and which may be treatable.

According to these data, eosinophilia may be one of the treatable causes in a small but significant proportion of patients with bronchiectasis. A trial of mepolizumab may be reasonable in patients inadequately controlled on inhaled anti-inflammatory drugs. “If they do not profit from this therapy, then stop,” she added.

Dr. Rademacher acknowledged that data from this small case series are “not enough to say that [mepolizumab] is an option for these patients,” but she believes the consistency of benefit in this small series will encourage the trials needed to confirm that this approach is safe and effective.

Dr. Rademacher reported no disclosures relevant to the report.

PARIS – Bronchiectasis responds to mepolizumab if the clinical profile includes eosinophilia, according to a small case series of patients presented as a late-breaking study at the annual congress of the European Respiratory Society.

Ted Bosworth/MDedge Newws

“The message is that it is important to think of all of the etiologies and treatable traits in patients with bronchiectasis, and do not forget eosinophilia, because this can be treated,” reported Jessica Rademacher, MD, of the Clinic for Pulmonology at Hannover (Germany) Medical School.

Mepolizumab is a monoclonal antibody that targets interleukin-5, an important signaling protein for eosinophil recruitment, and is approved for use in asthma with eosinophilia. Larger, controlled trials are needed to confirm its efficacy in bronchiectasis, but the clinical improvements after 6 months of treatment in a series of 12 patients at Dr. Rademacher’s center were impressive.

Bronchiectasis patients were selected for treatment with mepolizumab if they had been poorly controlled on conventional therapies and they had an eosinophil count of greater than 300 cells/mm³. Of 328 patients with bronchiectasis that are being followed at Dr. Rademacher’s center, 7% met these criteria. Dr. Rademacher presented data on 12 who had been followed for at least 6 months.

In these patients, the median eosinophil count fell from a median baseline of 1,000 cells/mm³ to 100 cells/mm³ at 6 months (P = .0012). The median annualized rate of exacerbations fell from three per year to one per year, and the median Modified Medical Research Council Dyspnea Scale score fell from 2 to 0 (P = .004).

“There was a steroid-sparing effect in all seven patients who were taking oral corticosteroids at baseline. Five stopped oral steroids completely,” Dr. Rademacher reported.

A visual analog scale ranging from 1 to 10 with higher scores representing improvement showed patient-rated quality of life improved from 4 to 6.5 (P = .01). Dr. Rademacher emphasized this outcome because “improved quality of life is really what we are trying to achieve.”

Mepolizumab was well tolerated. In one patient who developed pneumonia, mepolizumab was discontinued, but it was restarted when the infection resolved, because the pneumonia was not considered mepolizumab related.

Although Dr. Rademacher acknowledged the possibility that at least some of the patients in this case series had overlapping asthma, she emphasized that they were selected from a referral population that had a comprehensive workup and that this overlap has been rarely reported.

There is evidence that anti–interleukin-5 therapies such as mepolizumab are effective in respiratory diseases when eosinophilia is present, according to Dr. Rademacher. For example, she cited reports of clinical improvement in chronic obstructive pulmonary disease and granulomatosis with polyangiitis patients with high eosinophil counts. In bronchiectasis, which has many causes, it may be particularly important to select relevant targets.

“There is an important variability in the presentation of bronchiectasis. Not all these patients have reduced lung function,” she said. Rather, the most significant symptoms for a patient may be sputum or cough. She suggested that the goals are to identify underlying causes of symptoms and which may be treatable.

According to these data, eosinophilia may be one of the treatable causes in a small but significant proportion of patients with bronchiectasis. A trial of mepolizumab may be reasonable in patients inadequately controlled on inhaled anti-inflammatory drugs. “If they do not profit from this therapy, then stop,” she added.

Dr. Rademacher acknowledged that data from this small case series are “not enough to say that [mepolizumab] is an option for these patients,” but she believes the consistency of benefit in this small series will encourage the trials needed to confirm that this approach is safe and effective.

Dr. Rademacher reported no disclosures relevant to the report.

Discontinuing ibrutinib therapy because of disease progression was associated with worse survival, according to a real-world study of ibrutinib dosing in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma patients.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

Researchers at the University of Rochester Wilmot Cancer Institute in New York, who performed the single-center study, also found that optimal dosing early on in treatment has a significant impact on disease progression.

“Treating physicians need to be aware of these outcomes when initiating therapy on patients with high-risk CLL or lymphoma, as well as those with significant comorbidities or immune deficiencies,” AnnaLynn M. Williams. MS, and her colleagues reported in Clinical Lymphoma, Myeloma and Leukemia.

The researchers examined the impact of ibrutinib discontinuation and dose adherence on overall and progression-free survival in 170 patients with non-Hodgkin lymphoma and CLL treated with the drug at the Wilmot Cancer Institute between Jan. 1, 2014, and Dec. 1, 2016.

The study comprised 115 patients with CLL, 23 patients with Waldenstrom macroglobulinemia, 21 patients with mantle cell lymphoma, and 11 patients with other non-Hodgkin lymphomas. The median age of patients who started ibrutinib was 68 years, and the median treatment duration was 14.3 months. About a third of patients were taking ibrutinib as a first-line treatment.

Overall, 51 patients (30%) permanently discontinued ibrutinib during the study period, with more than half of the discontinuations stemming from adverse events or comorbidities. About 35% of the discontinuations were due to disease progression.

Median overall survival after discontinuation due to disease progression was 1.7 months. When patients discontinued for other reasons, median overall survival was not reached, compared with stopping for disease progression (P = .0008).

The researchers reported that among patients who discontinued for nonprogression reasons, 67% were alive after 1 year. Among CLL patients, 80% were alive after 1 year.

Among 20 patients who had a dose adherence of less than 80% in the first 8 weeks, the researchers found worse progression-free survival (P = .002) and overall survival (P = .021). Among CLL patients only, progression-free survival was significantly worse (P = .043) but overall survival was not (P = .816).

The study also included five patients who reduced their ibrutinib dose in the first 8 weeks – down to 280 mg in two patients, 140 mg in two patients, and 420 mg in one patient. Again, the researchers observed worse progression-free survival (P = .004) and overall survival (P = .014), compared with patients who maintained their dosing level.

Interrupting ibrutinib dosing had an impact on survival but not as much as discontinuation. Among 10 patients who interrupted therapy for more than a week and then restarted, progression-free survival was worse, compared with those who stayed on treatment continuously (P = .047), but overall survival was not significantly worse (P = .577).

“This would suggest that the ideal treatment strategy would be to recommend initiation of therapy at standard dosing and interruption as needed as directed in the [Food and Drug Administration] label,” the researchers wrote.

The study was funded by the National Cancer Institute and the Cadregari Endowment Fund. The researchers reported having no conflicts of interest.

[email protected]

SOURCE: Williams AM et al. Clin Lymphoma Myeloma Leuk. 2018 Oct 12. doi: 10.1016/j.clml.2018.10.005.

Discontinuing ibrutinib therapy because of disease progression was associated with worse survival, according to a real-world study of ibrutinib dosing in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma patients.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

Researchers at the University of Rochester Wilmot Cancer Institute in New York, who performed the single-center study, also found that optimal dosing early on in treatment has a significant impact on disease progression.

“Treating physicians need to be aware of these outcomes when initiating therapy on patients with high-risk CLL or lymphoma, as well as those with significant comorbidities or immune deficiencies,” AnnaLynn M. Williams. MS, and her colleagues reported in Clinical Lymphoma, Myeloma and Leukemia.

The researchers examined the impact of ibrutinib discontinuation and dose adherence on overall and progression-free survival in 170 patients with non-Hodgkin lymphoma and CLL treated with the drug at the Wilmot Cancer Institute between Jan. 1, 2014, and Dec. 1, 2016.

The study comprised 115 patients with CLL, 23 patients with Waldenstrom macroglobulinemia, 21 patients with mantle cell lymphoma, and 11 patients with other non-Hodgkin lymphomas. The median age of patients who started ibrutinib was 68 years, and the median treatment duration was 14.3 months. About a third of patients were taking ibrutinib as a first-line treatment.

Overall, 51 patients (30%) permanently discontinued ibrutinib during the study period, with more than half of the discontinuations stemming from adverse events or comorbidities. About 35% of the discontinuations were due to disease progression.

Median overall survival after discontinuation due to disease progression was 1.7 months. When patients discontinued for other reasons, median overall survival was not reached, compared with stopping for disease progression (P = .0008).

The researchers reported that among patients who discontinued for nonprogression reasons, 67% were alive after 1 year. Among CLL patients, 80% were alive after 1 year.

Among 20 patients who had a dose adherence of less than 80% in the first 8 weeks, the researchers found worse progression-free survival (P = .002) and overall survival (P = .021). Among CLL patients only, progression-free survival was significantly worse (P = .043) but overall survival was not (P = .816).

The study also included five patients who reduced their ibrutinib dose in the first 8 weeks – down to 280 mg in two patients, 140 mg in two patients, and 420 mg in one patient. Again, the researchers observed worse progression-free survival (P = .004) and overall survival (P = .014), compared with patients who maintained their dosing level.

Interrupting ibrutinib dosing had an impact on survival but not as much as discontinuation. Among 10 patients who interrupted therapy for more than a week and then restarted, progression-free survival was worse, compared with those who stayed on treatment continuously (P = .047), but overall survival was not significantly worse (P = .577).

“This would suggest that the ideal treatment strategy would be to recommend initiation of therapy at standard dosing and interruption as needed as directed in the [Food and Drug Administration] label,” the researchers wrote.

The study was funded by the National Cancer Institute and the Cadregari Endowment Fund. The researchers reported having no conflicts of interest.

[email protected]

SOURCE: Williams AM et al. Clin Lymphoma Myeloma Leuk. 2018 Oct 12. doi: 10.1016/j.clml.2018.10.005.

Discontinuing ibrutinib therapy because of disease progression was associated with worse survival, according to a real-world study of ibrutinib dosing in chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma patients.

Courtesy Wikimedia Commons/Nephron/Creative Commons BY-SA-3.0

Researchers at the University of Rochester Wilmot Cancer Institute in New York, who performed the single-center study, also found that optimal dosing early on in treatment has a significant impact on disease progression.

“Treating physicians need to be aware of these outcomes when initiating therapy on patients with high-risk CLL or lymphoma, as well as those with significant comorbidities or immune deficiencies,” AnnaLynn M. Williams. MS, and her colleagues reported in Clinical Lymphoma, Myeloma and Leukemia.

The researchers examined the impact of ibrutinib discontinuation and dose adherence on overall and progression-free survival in 170 patients with non-Hodgkin lymphoma and CLL treated with the drug at the Wilmot Cancer Institute between Jan. 1, 2014, and Dec. 1, 2016.

The study comprised 115 patients with CLL, 23 patients with Waldenstrom macroglobulinemia, 21 patients with mantle cell lymphoma, and 11 patients with other non-Hodgkin lymphomas. The median age of patients who started ibrutinib was 68 years, and the median treatment duration was 14.3 months. About a third of patients were taking ibrutinib as a first-line treatment.

Overall, 51 patients (30%) permanently discontinued ibrutinib during the study period, with more than half of the discontinuations stemming from adverse events or comorbidities. About 35% of the discontinuations were due to disease progression.

Median overall survival after discontinuation due to disease progression was 1.7 months. When patients discontinued for other reasons, median overall survival was not reached, compared with stopping for disease progression (P = .0008).

The researchers reported that among patients who discontinued for nonprogression reasons, 67% were alive after 1 year. Among CLL patients, 80% were alive after 1 year.

Among 20 patients who had a dose adherence of less than 80% in the first 8 weeks, the researchers found worse progression-free survival (P = .002) and overall survival (P = .021). Among CLL patients only, progression-free survival was significantly worse (P = .043) but overall survival was not (P = .816).

The study also included five patients who reduced their ibrutinib dose in the first 8 weeks – down to 280 mg in two patients, 140 mg in two patients, and 420 mg in one patient. Again, the researchers observed worse progression-free survival (P = .004) and overall survival (P = .014), compared with patients who maintained their dosing level.

Interrupting ibrutinib dosing had an impact on survival but not as much as discontinuation. Among 10 patients who interrupted therapy for more than a week and then restarted, progression-free survival was worse, compared with those who stayed on treatment continuously (P = .047), but overall survival was not significantly worse (P = .577).

“This would suggest that the ideal treatment strategy would be to recommend initiation of therapy at standard dosing and interruption as needed as directed in the [Food and Drug Administration] label,” the researchers wrote.

The study was funded by the National Cancer Institute and the Cadregari Endowment Fund. The researchers reported having no conflicts of interest.

[email protected]

SOURCE: Williams AM et al. Clin Lymphoma Myeloma Leuk. 2018 Oct 12. doi: 10.1016/j.clml.2018.10.005.

Throughout medical training, you learn to write complete and detailed notes to communicate with other physicians. As a student and resident, you are praised when you succinctly analyze and address all patient problems while justifying your orders for the day. But notes do not exist just to document patient care; they are the template by which our actual quality of care is judged and our patients’ severity of illness is captured.

Like it or not, ICD-10 coding, documentation, denials, calls, and emails from administrators are integral parts of a hospitalist’s day-to-day job. Why? The specificity and comprehensiveness of diagnoses affect such metrics as hospital length of stay, mortality, and Case Mix Index documentation.

Good documentation can lead to better severity of illness (SOI) and risk of mortality (ROM) scores, better patient safety indicator (PSI) scores, better Healthgrades scores, better University Hospital Consortium (UHC) scores, and decreased Recovery Audit Contractor (RAC) denials as well as appropriate reimbursement. Good documentation can even lead to improved patient care and better perceived treatment outcomes.

It is no surprise that many hospital administrators invest time and money in staff to support the proper usage of language in your notes. Of course, sometimes these well-meaning “queries” can throw you into emotional turmoil as you try to understand what was not clear in your excellent note about your patient’s heart failure exacerbation. In this article, we will try to help you take your specificity and comprehensiveness of diagnoses to the next level.
 

Basics of billing

Physicians do not need to become coders but it is helpful to have some understanding of what happens behind the scenes. Not everyone realizes that physician billing is completely different from hospital billing. Physician billing pertains to the care provided by the clinician, whereas hospital billing pertains to the overall care the patient received.

Below is an example of a case of pneumonia, (see Table 1) which shows the importance of specificity. Just by specifying ‘Aspiration’ for the type of pneumonia, we increased the SOI and the expected ROM appropriately. Also see a change in relative weight (RW): Each diagnosis-related group (DRG) is assigned a relative weight = estimated use of resources, and payment per case is based on estimated resource consumption = relative weight x “blended rate for each hospital.”

• Use the terms “probable,” “possible,” “suspected,” or “likely” in documenting uncertain diagnoses (i.e., conditions for which physicians find clinical evidence that leads to a suspicion but not a definitive diagnosis). If conditions are ruled out or confirmed, clearly state so. If it remains uncertain, remember to carry this “possible” or “probable” diagnosis all the way through to the discharge summary or final progress note.
• Use linking of diagnoses when appropriate. For example, if the patient’s neuropathy, nephropathy, and retinopathy are related to their uncontrolled insulin dependent diabetes, state “uncontrolled insulin-dependent DMII with A_1c of 11 complicated with nephropathy, neuropathy, and retinopathy.” The coders cannot link these diagnoses, and when you link them, you show a higher complexity of your patient. Remember to link the diagnoses only when they are truly related – this is where your medical knowledge and expertise come into play.
• Use the highest specificity of evidence that supports your medical decision making. You don’t need to be too verbose, all you need is evidence supporting your medical decision making and treatment plan. Think of it as demonstrating the logic of your diagnosis to another physician.
• Use Acuity (acute, chronic, acute on chronic, mild, moderate, severe, etc.) per diagnosis. For example, if you say heart failure exacerbation, it makes perfect sense to your medical colleagues, but in the coding world, it means nothing. Specify if it is acute, or acute on chronic, heart failure.
• Use status of each diagnosis. Is the condition improving, worsening, or resolved? Status does not have to be mentioned in all progress notes. Try to include this descriptor in the discharge summary and the day of the event.
• Always document the clinical significance of any abnormal laboratory, radiology reports, or pathology finding. Coders cannot use test results as a basis for coding unless a clinician has reviewed, interpreted, and documented the significance of the results in the progress note. Simply copying and pasting a report in the notes is not considered clinical acknowledgment. Shorthand notes like “Na=150, start hydration with 0.45% saline” is not acceptable. The actual diagnosis has to be written (i.e. “hypernatremia”). In addition, coders cannot code from nursing, dietitian, respiratory, and physical therapy notes. For example, if nursing documents that a patient has a pressure ulcer the clinician must still document the diagnosis of pressure ulcer, location, and stage. Although dietitian notes may state a body mass index greater than 40, coders cannot assume that patient is morbidly obese. Physician documentation is needed to support the obesity code assignment.
• Document all conditions that affect the patient’s stay, including complications and chronic conditions for which medications have been ordered. These secondary diagnoses paint the most accurate clinical picture and provide information needed to calculate important data, such as complexity and severity of patient illness and mortality risk. A patient with community-acquired pneumonia without other comorbidities requires fewer resources and has a greater chance of a good outcome than does the same patient with complications, such as acute heart failure.
• Downcoding brings losses, upcoding brings fines. Exaggerating the severity of patient conditions can lead to payer audits, reimbursement take backs, and charges of abuse and fraudulent billing. Never stretch the truth. Make sure you can support every diagnosis in the patient’s chart using clinical criteria.

Dr. Rajda is medical director of clinical documentation and quality improvement for Mount Sinai Hospital in New York, and medical director for DRG appeals for the Mount Sinai Health System. She serves as assistant professor of medicine at Icahn School of Medicine at Mount Sinai. Dr. Fatemi is an assistant professor at the University of New Mexico, Albuquerque. She is director of documentation, coding, and billing for the division of hospital medicine at UNM. Dr. Reyna is assistant professor in the division of hospital medicine and medical director for clinical documentation and quality improvement at Mount Sinai Medical Center.

Throughout medical training, you learn to write complete and detailed notes to communicate with other physicians. As a student and resident, you are praised when you succinctly analyze and address all patient problems while justifying your orders for the day. But notes do not exist just to document patient care; they are the template by which our actual quality of care is judged and our patients’ severity of illness is captured.

Like it or not, ICD-10 coding, documentation, denials, calls, and emails from administrators are integral parts of a hospitalist’s day-to-day job. Why? The specificity and comprehensiveness of diagnoses affect such metrics as hospital length of stay, mortality, and Case Mix Index documentation.

Good documentation can lead to better severity of illness (SOI) and risk of mortality (ROM) scores, better patient safety indicator (PSI) scores, better Healthgrades scores, better University Hospital Consortium (UHC) scores, and decreased Recovery Audit Contractor (RAC) denials as well as appropriate reimbursement. Good documentation can even lead to improved patient care and better perceived treatment outcomes.

It is no surprise that many hospital administrators invest time and money in staff to support the proper usage of language in your notes. Of course, sometimes these well-meaning “queries” can throw you into emotional turmoil as you try to understand what was not clear in your excellent note about your patient’s heart failure exacerbation. In this article, we will try to help you take your specificity and comprehensiveness of diagnoses to the next level.
 

Basics of billing

Physicians do not need to become coders but it is helpful to have some understanding of what happens behind the scenes. Not everyone realizes that physician billing is completely different from hospital billing. Physician billing pertains to the care provided by the clinician, whereas hospital billing pertains to the overall care the patient received.

Below is an example of a case of pneumonia, (see Table 1) which shows the importance of specificity. Just by specifying ‘Aspiration’ for the type of pneumonia, we increased the SOI and the expected ROM appropriately. Also see a change in relative weight (RW): Each diagnosis-related group (DRG) is assigned a relative weight = estimated use of resources, and payment per case is based on estimated resource consumption = relative weight x “blended rate for each hospital.”

• Use the terms “probable,” “possible,” “suspected,” or “likely” in documenting uncertain diagnoses (i.e., conditions for which physicians find clinical evidence that leads to a suspicion but not a definitive diagnosis). If conditions are ruled out or confirmed, clearly state so. If it remains uncertain, remember to carry this “possible” or “probable” diagnosis all the way through to the discharge summary or final progress note.
• Use linking of diagnoses when appropriate. For example, if the patient’s neuropathy, nephropathy, and retinopathy are related to their uncontrolled insulin dependent diabetes, state “uncontrolled insulin-dependent DMII with A_1c of 11 complicated with nephropathy, neuropathy, and retinopathy.” The coders cannot link these diagnoses, and when you link them, you show a higher complexity of your patient. Remember to link the diagnoses only when they are truly related – this is where your medical knowledge and expertise come into play.
• Use the highest specificity of evidence that supports your medical decision making. You don’t need to be too verbose, all you need is evidence supporting your medical decision making and treatment plan. Think of it as demonstrating the logic of your diagnosis to another physician.
• Use Acuity (acute, chronic, acute on chronic, mild, moderate, severe, etc.) per diagnosis. For example, if you say heart failure exacerbation, it makes perfect sense to your medical colleagues, but in the coding world, it means nothing. Specify if it is acute, or acute on chronic, heart failure.
• Use status of each diagnosis. Is the condition improving, worsening, or resolved? Status does not have to be mentioned in all progress notes. Try to include this descriptor in the discharge summary and the day of the event.
• Always document the clinical significance of any abnormal laboratory, radiology reports, or pathology finding. Coders cannot use test results as a basis for coding unless a clinician has reviewed, interpreted, and documented the significance of the results in the progress note. Simply copying and pasting a report in the notes is not considered clinical acknowledgment. Shorthand notes like “Na=150, start hydration with 0.45% saline” is not acceptable. The actual diagnosis has to be written (i.e. “hypernatremia”). In addition, coders cannot code from nursing, dietitian, respiratory, and physical therapy notes. For example, if nursing documents that a patient has a pressure ulcer the clinician must still document the diagnosis of pressure ulcer, location, and stage. Although dietitian notes may state a body mass index greater than 40, coders cannot assume that patient is morbidly obese. Physician documentation is needed to support the obesity code assignment.
• Document all conditions that affect the patient’s stay, including complications and chronic conditions for which medications have been ordered. These secondary diagnoses paint the most accurate clinical picture and provide information needed to calculate important data, such as complexity and severity of patient illness and mortality risk. A patient with community-acquired pneumonia without other comorbidities requires fewer resources and has a greater chance of a good outcome than does the same patient with complications, such as acute heart failure.
• Downcoding brings losses, upcoding brings fines. Exaggerating the severity of patient conditions can lead to payer audits, reimbursement take backs, and charges of abuse and fraudulent billing. Never stretch the truth. Make sure you can support every diagnosis in the patient’s chart using clinical criteria.

Dr. Rajda is medical director of clinical documentation and quality improvement for Mount Sinai Hospital in New York, and medical director for DRG appeals for the Mount Sinai Health System. She serves as assistant professor of medicine at Icahn School of Medicine at Mount Sinai. Dr. Fatemi is an assistant professor at the University of New Mexico, Albuquerque. She is director of documentation, coding, and billing for the division of hospital medicine at UNM. Dr. Reyna is assistant professor in the division of hospital medicine and medical director for clinical documentation and quality improvement at Mount Sinai Medical Center.

Throughout medical training, you learn to write complete and detailed notes to communicate with other physicians. As a student and resident, you are praised when you succinctly analyze and address all patient problems while justifying your orders for the day. But notes do not exist just to document patient care; they are the template by which our actual quality of care is judged and our patients’ severity of illness is captured.

Like it or not, ICD-10 coding, documentation, denials, calls, and emails from administrators are integral parts of a hospitalist’s day-to-day job. Why? The specificity and comprehensiveness of diagnoses affect such metrics as hospital length of stay, mortality, and Case Mix Index documentation.

Good documentation can lead to better severity of illness (SOI) and risk of mortality (ROM) scores, better patient safety indicator (PSI) scores, better Healthgrades scores, better University Hospital Consortium (UHC) scores, and decreased Recovery Audit Contractor (RAC) denials as well as appropriate reimbursement. Good documentation can even lead to improved patient care and better perceived treatment outcomes.

It is no surprise that many hospital administrators invest time and money in staff to support the proper usage of language in your notes. Of course, sometimes these well-meaning “queries” can throw you into emotional turmoil as you try to understand what was not clear in your excellent note about your patient’s heart failure exacerbation. In this article, we will try to help you take your specificity and comprehensiveness of diagnoses to the next level.
 

Basics of billing

Physicians do not need to become coders but it is helpful to have some understanding of what happens behind the scenes. Not everyone realizes that physician billing is completely different from hospital billing. Physician billing pertains to the care provided by the clinician, whereas hospital billing pertains to the overall care the patient received.

Below is an example of a case of pneumonia, (see Table 1) which shows the importance of specificity. Just by specifying ‘Aspiration’ for the type of pneumonia, we increased the SOI and the expected ROM appropriately. Also see a change in relative weight (RW): Each diagnosis-related group (DRG) is assigned a relative weight = estimated use of resources, and payment per case is based on estimated resource consumption = relative weight x “blended rate for each hospital.”

• Use the terms “probable,” “possible,” “suspected,” or “likely” in documenting uncertain diagnoses (i.e., conditions for which physicians find clinical evidence that leads to a suspicion but not a definitive diagnosis). If conditions are ruled out or confirmed, clearly state so. If it remains uncertain, remember to carry this “possible” or “probable” diagnosis all the way through to the discharge summary or final progress note.
• Use linking of diagnoses when appropriate. For example, if the patient’s neuropathy, nephropathy, and retinopathy are related to their uncontrolled insulin dependent diabetes, state “uncontrolled insulin-dependent DMII with A_1c of 11 complicated with nephropathy, neuropathy, and retinopathy.” The coders cannot link these diagnoses, and when you link them, you show a higher complexity of your patient. Remember to link the diagnoses only when they are truly related – this is where your medical knowledge and expertise come into play.
• Use the highest specificity of evidence that supports your medical decision making. You don’t need to be too verbose, all you need is evidence supporting your medical decision making and treatment plan. Think of it as demonstrating the logic of your diagnosis to another physician.
• Use Acuity (acute, chronic, acute on chronic, mild, moderate, severe, etc.) per diagnosis. For example, if you say heart failure exacerbation, it makes perfect sense to your medical colleagues, but in the coding world, it means nothing. Specify if it is acute, or acute on chronic, heart failure.
• Use status of each diagnosis. Is the condition improving, worsening, or resolved? Status does not have to be mentioned in all progress notes. Try to include this descriptor in the discharge summary and the day of the event.
• Always document the clinical significance of any abnormal laboratory, radiology reports, or pathology finding. Coders cannot use test results as a basis for coding unless a clinician has reviewed, interpreted, and documented the significance of the results in the progress note. Simply copying and pasting a report in the notes is not considered clinical acknowledgment. Shorthand notes like “Na=150, start hydration with 0.45% saline” is not acceptable. The actual diagnosis has to be written (i.e. “hypernatremia”). In addition, coders cannot code from nursing, dietitian, respiratory, and physical therapy notes. For example, if nursing documents that a patient has a pressure ulcer the clinician must still document the diagnosis of pressure ulcer, location, and stage. Although dietitian notes may state a body mass index greater than 40, coders cannot assume that patient is morbidly obese. Physician documentation is needed to support the obesity code assignment.
• Document all conditions that affect the patient’s stay, including complications and chronic conditions for which medications have been ordered. These secondary diagnoses paint the most accurate clinical picture and provide information needed to calculate important data, such as complexity and severity of patient illness and mortality risk. A patient with community-acquired pneumonia without other comorbidities requires fewer resources and has a greater chance of a good outcome than does the same patient with complications, such as acute heart failure.
• Downcoding brings losses, upcoding brings fines. Exaggerating the severity of patient conditions can lead to payer audits, reimbursement take backs, and charges of abuse and fraudulent billing. Never stretch the truth. Make sure you can support every diagnosis in the patient’s chart using clinical criteria.

Dr. Rajda is medical director of clinical documentation and quality improvement for Mount Sinai Hospital in New York, and medical director for DRG appeals for the Mount Sinai Health System. She serves as assistant professor of medicine at Icahn School of Medicine at Mount Sinai. Dr. Fatemi is an assistant professor at the University of New Mexico, Albuquerque. She is director of documentation, coding, and billing for the division of hospital medicine at UNM. Dr. Reyna is assistant professor in the division of hospital medicine and medical director for clinical documentation and quality improvement at Mount Sinai Medical Center.

Multiple studies clearly demonstrate triggers in episodic migraine, often related to change in homeostasis or environment, according to a recent investigation. Furthermore, many common migraine triggers are not easily modifiable, and avoiding triggers may not be realistic. However, healthy lifestyle choices such as exercise, adequate sleep, stress management, and eating regularly may prevent triggers and transformation to chronic migraine over time. Multiple migraine attack triggers have been established based on patient surveys, diary studies, and clinical trials. Key points include:

• Stress, menstrual cycle changes, weather changes, sleep disturbances, alcohol, and other foods are among the most common factors mentioned.
• Clinical studies have also verified that fasting, premenstrual periods in women, “letdown” after stress, and most likely low barometric pressures are migraine triggers.
• Premonitory symptoms such as neck pain, fatigue, and sensitivity to lights, sounds, or odors may mimic triggers.

Marmura MJ. Triggers, protectors, and predictors in episodic migraine. Curr Pain Headache Rep. 2018;22:81. doi:10.1007/s11916-018-0734-0.

Multiple studies clearly demonstrate triggers in episodic migraine, often related to change in homeostasis or environment, according to a recent investigation. Furthermore, many common migraine triggers are not easily modifiable, and avoiding triggers may not be realistic. However, healthy lifestyle choices such as exercise, adequate sleep, stress management, and eating regularly may prevent triggers and transformation to chronic migraine over time. Multiple migraine attack triggers have been established based on patient surveys, diary studies, and clinical trials. Key points include:

• Stress, menstrual cycle changes, weather changes, sleep disturbances, alcohol, and other foods are among the most common factors mentioned.
• Clinical studies have also verified that fasting, premenstrual periods in women, “letdown” after stress, and most likely low barometric pressures are migraine triggers.
• Premonitory symptoms such as neck pain, fatigue, and sensitivity to lights, sounds, or odors may mimic triggers.

Marmura MJ. Triggers, protectors, and predictors in episodic migraine. Curr Pain Headache Rep. 2018;22:81. doi:10.1007/s11916-018-0734-0.

Multiple studies clearly demonstrate triggers in episodic migraine, often related to change in homeostasis or environment, according to a recent investigation. Furthermore, many common migraine triggers are not easily modifiable, and avoiding triggers may not be realistic. However, healthy lifestyle choices such as exercise, adequate sleep, stress management, and eating regularly may prevent triggers and transformation to chronic migraine over time. Multiple migraine attack triggers have been established based on patient surveys, diary studies, and clinical trials. Key points include:

• Stress, menstrual cycle changes, weather changes, sleep disturbances, alcohol, and other foods are among the most common factors mentioned.
• Clinical studies have also verified that fasting, premenstrual periods in women, “letdown” after stress, and most likely low barometric pressures are migraine triggers.
• Premonitory symptoms such as neck pain, fatigue, and sensitivity to lights, sounds, or odors may mimic triggers.

Marmura MJ. Triggers, protectors, and predictors in episodic migraine. Curr Pain Headache Rep. 2018;22:81. doi:10.1007/s11916-018-0734-0.

A recent genome-wide association study (GWAS) provides new insights into the genetic basis of childhood migraine and allows for precision therapeutic development strategies targeting migraine patients of African-American ancestry. Researchers conducted a GWAS of 380 African-American children and 2129 ancestry-matched controls to identify variants associated with migraine. They then attempted to replicate their primary analysis in an independent cohort of 233 African-American patients and 4038 non-migraine control subjects. They found:

• Common variants at 5q33.1 are associated with migraine risk in African-American children.
• The association was validated in an independent study for an overall meta-analysis P-value of 3.81×10⁻¹⁰.
• eQTL (expression quantitative trait loci) analysis of the Genotype-Tissue Expression data also shows the genotypes of rs72793414 were strongly correlated with the mRNA expression levels of NMUR2 at 5q33.1.

Chang X, Pellegrino R, Garifallou, et al. Common variants at 5q33.1 predispose to migraine in African-American children. [Published online ahead of print September 28, 2018]. J Med Genet. doi:10.1136/jmedgenet-2018-105359.

A recent genome-wide association study (GWAS) provides new insights into the genetic basis of childhood migraine and allows for precision therapeutic development strategies targeting migraine patients of African-American ancestry. Researchers conducted a GWAS of 380 African-American children and 2129 ancestry-matched controls to identify variants associated with migraine. They then attempted to replicate their primary analysis in an independent cohort of 233 African-American patients and 4038 non-migraine control subjects. They found:

• Common variants at 5q33.1 are associated with migraine risk in African-American children.
• The association was validated in an independent study for an overall meta-analysis P-value of 3.81×10⁻¹⁰.
• eQTL (expression quantitative trait loci) analysis of the Genotype-Tissue Expression data also shows the genotypes of rs72793414 were strongly correlated with the mRNA expression levels of NMUR2 at 5q33.1.

Chang X, Pellegrino R, Garifallou, et al. Common variants at 5q33.1 predispose to migraine in African-American children. [Published online ahead of print September 28, 2018]. J Med Genet. doi:10.1136/jmedgenet-2018-105359.

A recent genome-wide association study (GWAS) provides new insights into the genetic basis of childhood migraine and allows for precision therapeutic development strategies targeting migraine patients of African-American ancestry. Researchers conducted a GWAS of 380 African-American children and 2129 ancestry-matched controls to identify variants associated with migraine. They then attempted to replicate their primary analysis in an independent cohort of 233 African-American patients and 4038 non-migraine control subjects. They found:

• Common variants at 5q33.1 are associated with migraine risk in African-American children.
• The association was validated in an independent study for an overall meta-analysis P-value of 3.81×10⁻¹⁰.
• eQTL (expression quantitative trait loci) analysis of the Genotype-Tissue Expression data also shows the genotypes of rs72793414 were strongly correlated with the mRNA expression levels of NMUR2 at 5q33.1.

Chang X, Pellegrino R, Garifallou, et al. Common variants at 5q33.1 predispose to migraine in African-American children. [Published online ahead of print September 28, 2018]. J Med Genet. doi:10.1136/jmedgenet-2018-105359.

The current diagnostic criteria for migraine outlined in the 3rd version of the International Classification of Headache Disorders (ICHD) are far more sensitive and specific than the clinical criteria proposed in 1962. This is according to a recent review that examines how the diagnostic criteria for migraine have evolved during the past 45 years and evaluates the strengths and weaknesses of the current diagnostic criteria promulgated by the ICHD. In future iterations, dividing episodic and chronic migraine into subtypes based on frequency (ie, low frequency vs high frequency; near-daily vs daily) potentially could assist in guiding clinical management. In addition, a better understanding of aura, vestibular migraine, migrainous infarction, and hemiplegic migraine likely will lead to more refined diagnostic criteria for those entities. As the pathophysiology of migraine is more fully elucidated and more sophisticated diagnostic technologies are developed (eg, the identification of biomarkers), the current diagnostic criteria for migraine will likely be further refined. Furthermore, the ICHD has allowed for more precise research study design in the field of headache medicine.

Tinsley A. Rothrock JF. What are we missing in the diagnostic criteria for migraine? Curr Pain Headache Rep. 2018;22:84. doi:10.1007/s11916-018-0733-1.

The current diagnostic criteria for migraine outlined in the 3rd version of the International Classification of Headache Disorders (ICHD) are far more sensitive and specific than the clinical criteria proposed in 1962. This is according to a recent review that examines how the diagnostic criteria for migraine have evolved during the past 45 years and evaluates the strengths and weaknesses of the current diagnostic criteria promulgated by the ICHD. In future iterations, dividing episodic and chronic migraine into subtypes based on frequency (ie, low frequency vs high frequency; near-daily vs daily) potentially could assist in guiding clinical management. In addition, a better understanding of aura, vestibular migraine, migrainous infarction, and hemiplegic migraine likely will lead to more refined diagnostic criteria for those entities. As the pathophysiology of migraine is more fully elucidated and more sophisticated diagnostic technologies are developed (eg, the identification of biomarkers), the current diagnostic criteria for migraine will likely be further refined. Furthermore, the ICHD has allowed for more precise research study design in the field of headache medicine.

Tinsley A. Rothrock JF. What are we missing in the diagnostic criteria for migraine? Curr Pain Headache Rep. 2018;22:84. doi:10.1007/s11916-018-0733-1.

The current diagnostic criteria for migraine outlined in the 3rd version of the International Classification of Headache Disorders (ICHD) are far more sensitive and specific than the clinical criteria proposed in 1962. This is according to a recent review that examines how the diagnostic criteria for migraine have evolved during the past 45 years and evaluates the strengths and weaknesses of the current diagnostic criteria promulgated by the ICHD. In future iterations, dividing episodic and chronic migraine into subtypes based on frequency (ie, low frequency vs high frequency; near-daily vs daily) potentially could assist in guiding clinical management. In addition, a better understanding of aura, vestibular migraine, migrainous infarction, and hemiplegic migraine likely will lead to more refined diagnostic criteria for those entities. As the pathophysiology of migraine is more fully elucidated and more sophisticated diagnostic technologies are developed (eg, the identification of biomarkers), the current diagnostic criteria for migraine will likely be further refined. Furthermore, the ICHD has allowed for more precise research study design in the field of headache medicine.

Tinsley A. Rothrock JF. What are we missing in the diagnostic criteria for migraine? Curr Pain Headache Rep. 2018;22:84. doi:10.1007/s11916-018-0733-1.

san francisco – A new tuberculosis vaccine showed promise in a phase 2b trial, including efficacy in adults and subjects who were already exposed to TB. The vaccine showed efficacy in young adults – an important finding because models suggest that inducing immunity in adolescents and young adults would be the fastest and most cost-effective approach to dealing with the global TB epidemic.

CDC/Janice Carr

The study recruited adults who had previously been exposed to Mycobacterium tuberculosis, a population that receives no benefit from the long-standing bacillus Calmette-Guérin (BCG) vaccine. The overall efficacy of protection was 54%. “There isn’t any vaccine that’s been demonstrated to work in people who are already infected. It’s also the first vaccine to show this level of statistically significant protection in adults, and it’s adults who are the major transmitters of tuberculosis. The modeling has shown that even a vaccine that could protect infected adults at 20% vaccine efficacy would have a substantial impact on the epidemic and be cost effective,” said Ann Ginsberg, MD, PhD, chief medical officer at Aeras, which developed the vaccine and is now testing it in partnership with GlaxoSmithKline.

The results of the study were presented at ID Week 2018 and published in the New England Journal of Medicine (2018 Sep 25. doi: 10.1056/NEJMoa1803484).

The results address a major weakness of the BCG vaccine, which is that some studies have shown it offers little benefit to subjects who are already infected with the disease, which is the case for about a quarter of the world’s population, according to Dr. Ginsberg. The probable explanation is that previous infection with M. tuberculosis or a related bacteria is common in some populations and that this exposure grants some protection against progression to active disease.

The researchers tested the M72/AS01E vaccine, which includes two M. tuberculosis antigens that were identified from patients who had controlled their infection and also the AS01 adjuvant, which contains two immunostimulating agents and is a component of a developmental malaria vaccine and the recombinant zoster vaccine Shingrix.

In Kenya, South Africa, and Zambia, the researchers randomized 3,330 participants (mean age, 28.9 years; 43% female) to receive two doses 1 month apart of either vaccine or placebo. After a mean follow-up of 2.3 years, the protocol efficacy analysis showed that the vaccine had an efficacy rate of 54.0% (P = .04) for pulmonary tuberculosis.

The vaccine had greater efficacy in men (75.2%; P = .03) than it did in women (27.4%; P = .52) and among individuals aged 25 years or younger (84.4%; P = .01) than it did among older subjects (10.2%, P = .82).

The frequency of serious adverse events was similar between the vaccine (1.6%) and the placebo group (1.8%). Unsolicited reports of adverse events were more common in the vaccine group than the placebo group (67.4% vs. 45.4%, respectively), driven largely by more reports of injection site reactions and flu-like symptoms. Solicited reports of adverse events were highlighted by a greater frequency of injection site pain in the vaccine group (81.8% vs. 34.4%). A total of 24.3% of the vaccine recipients reported grade 3 pain, compared with 3.3% in the placebo arm. Rates of fatigue, headache, malaise, or myalgia were also higher in the vaccine group, as was fever.

All of the subjects in the vaccine group had seroconversion at month 2, and 99% remained seroconverted at 12 months.

Next, the researchers plan to conduct studies in HIV-infected individuals and to proceed with phase III trials.

The trial was funded by GlaxoSmithKline Biologicals and Aeras. Dr. Ginsberg is an employee of Aeras.

SOURCE: Ginsberg A et al. IDWeek 2018, Abstract 120

san francisco – A new tuberculosis vaccine showed promise in a phase 2b trial, including efficacy in adults and subjects who were already exposed to TB. The vaccine showed efficacy in young adults – an important finding because models suggest that inducing immunity in adolescents and young adults would be the fastest and most cost-effective approach to dealing with the global TB epidemic.

CDC/Janice Carr

The study recruited adults who had previously been exposed to Mycobacterium tuberculosis, a population that receives no benefit from the long-standing bacillus Calmette-Guérin (BCG) vaccine. The overall efficacy of protection was 54%. “There isn’t any vaccine that’s been demonstrated to work in people who are already infected. It’s also the first vaccine to show this level of statistically significant protection in adults, and it’s adults who are the major transmitters of tuberculosis. The modeling has shown that even a vaccine that could protect infected adults at 20% vaccine efficacy would have a substantial impact on the epidemic and be cost effective,” said Ann Ginsberg, MD, PhD, chief medical officer at Aeras, which developed the vaccine and is now testing it in partnership with GlaxoSmithKline.

The results of the study were presented at ID Week 2018 and published in the New England Journal of Medicine (2018 Sep 25. doi: 10.1056/NEJMoa1803484).

The results address a major weakness of the BCG vaccine, which is that some studies have shown it offers little benefit to subjects who are already infected with the disease, which is the case for about a quarter of the world’s population, according to Dr. Ginsberg. The probable explanation is that previous infection with M. tuberculosis or a related bacteria is common in some populations and that this exposure grants some protection against progression to active disease.

The researchers tested the M72/AS01E vaccine, which includes two M. tuberculosis antigens that were identified from patients who had controlled their infection and also the AS01 adjuvant, which contains two immunostimulating agents and is a component of a developmental malaria vaccine and the recombinant zoster vaccine Shingrix.

In Kenya, South Africa, and Zambia, the researchers randomized 3,330 participants (mean age, 28.9 years; 43% female) to receive two doses 1 month apart of either vaccine or placebo. After a mean follow-up of 2.3 years, the protocol efficacy analysis showed that the vaccine had an efficacy rate of 54.0% (P = .04) for pulmonary tuberculosis.

The vaccine had greater efficacy in men (75.2%; P = .03) than it did in women (27.4%; P = .52) and among individuals aged 25 years or younger (84.4%; P = .01) than it did among older subjects (10.2%, P = .82).

The frequency of serious adverse events was similar between the vaccine (1.6%) and the placebo group (1.8%). Unsolicited reports of adverse events were more common in the vaccine group than the placebo group (67.4% vs. 45.4%, respectively), driven largely by more reports of injection site reactions and flu-like symptoms. Solicited reports of adverse events were highlighted by a greater frequency of injection site pain in the vaccine group (81.8% vs. 34.4%). A total of 24.3% of the vaccine recipients reported grade 3 pain, compared with 3.3% in the placebo arm. Rates of fatigue, headache, malaise, or myalgia were also higher in the vaccine group, as was fever.

All of the subjects in the vaccine group had seroconversion at month 2, and 99% remained seroconverted at 12 months.

Next, the researchers plan to conduct studies in HIV-infected individuals and to proceed with phase III trials.

The trial was funded by GlaxoSmithKline Biologicals and Aeras. Dr. Ginsberg is an employee of Aeras.

SOURCE: Ginsberg A et al. IDWeek 2018, Abstract 120

san francisco – A new tuberculosis vaccine showed promise in a phase 2b trial, including efficacy in adults and subjects who were already exposed to TB. The vaccine showed efficacy in young adults – an important finding because models suggest that inducing immunity in adolescents and young adults would be the fastest and most cost-effective approach to dealing with the global TB epidemic.

CDC/Janice Carr

The study recruited adults who had previously been exposed to Mycobacterium tuberculosis, a population that receives no benefit from the long-standing bacillus Calmette-Guérin (BCG) vaccine. The overall efficacy of protection was 54%. “There isn’t any vaccine that’s been demonstrated to work in people who are already infected. It’s also the first vaccine to show this level of statistically significant protection in adults, and it’s adults who are the major transmitters of tuberculosis. The modeling has shown that even a vaccine that could protect infected adults at 20% vaccine efficacy would have a substantial impact on the epidemic and be cost effective,” said Ann Ginsberg, MD, PhD, chief medical officer at Aeras, which developed the vaccine and is now testing it in partnership with GlaxoSmithKline.

The results of the study were presented at ID Week 2018 and published in the New England Journal of Medicine (2018 Sep 25. doi: 10.1056/NEJMoa1803484).

The results address a major weakness of the BCG vaccine, which is that some studies have shown it offers little benefit to subjects who are already infected with the disease, which is the case for about a quarter of the world’s population, according to Dr. Ginsberg. The probable explanation is that previous infection with M. tuberculosis or a related bacteria is common in some populations and that this exposure grants some protection against progression to active disease.

The researchers tested the M72/AS01E vaccine, which includes two M. tuberculosis antigens that were identified from patients who had controlled their infection and also the AS01 adjuvant, which contains two immunostimulating agents and is a component of a developmental malaria vaccine and the recombinant zoster vaccine Shingrix.

In Kenya, South Africa, and Zambia, the researchers randomized 3,330 participants (mean age, 28.9 years; 43% female) to receive two doses 1 month apart of either vaccine or placebo. After a mean follow-up of 2.3 years, the protocol efficacy analysis showed that the vaccine had an efficacy rate of 54.0% (P = .04) for pulmonary tuberculosis.

The vaccine had greater efficacy in men (75.2%; P = .03) than it did in women (27.4%; P = .52) and among individuals aged 25 years or younger (84.4%; P = .01) than it did among older subjects (10.2%, P = .82).

The frequency of serious adverse events was similar between the vaccine (1.6%) and the placebo group (1.8%). Unsolicited reports of adverse events were more common in the vaccine group than the placebo group (67.4% vs. 45.4%, respectively), driven largely by more reports of injection site reactions and flu-like symptoms. Solicited reports of adverse events were highlighted by a greater frequency of injection site pain in the vaccine group (81.8% vs. 34.4%). A total of 24.3% of the vaccine recipients reported grade 3 pain, compared with 3.3% in the placebo arm. Rates of fatigue, headache, malaise, or myalgia were also higher in the vaccine group, as was fever.

All of the subjects in the vaccine group had seroconversion at month 2, and 99% remained seroconverted at 12 months.

Next, the researchers plan to conduct studies in HIV-infected individuals and to proceed with phase III trials.

The trial was funded by GlaxoSmithKline Biologicals and Aeras. Dr. Ginsberg is an employee of Aeras.

SOURCE: Ginsberg A et al. IDWeek 2018, Abstract 120

PHILADELPHIA – Use of etrasimod was associated with improved clinical and endoscopic results, and was generally safe and well tolerated compared with placebo in patients with moderate to severe ulcerative colitis, according to a recent award-winning presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

“Patients with moderate to severe ulcerative colitis receiving etrasimod 2 mg per day achieved statistically significant and clinically meaningful differences in all of the primary and secondary endpoints, and most exploratory endpoints were also significantly proved,” William J. Sandborn, MD, AGAF, FACG, professor of clinical medicine at the University of California, San Diego, stated in his presentation at the meeting. “A dose-response relationship was observed in virtually all of the measures of treatment efficacy.”

The abstract received the ACG Auxiliary Award (Member), which is given to ACG members each year with outstanding abstract submissions.

Dr. Sandborn and his colleagues enrolled 156 patients with ulcerative colitis (UC) into the OASIS study, a randomized, double-blind, parallel-group, phase 2 study of etrasimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, compared with placebo. Patients were aged 18-80 years, with moderate to severe UC as defined by a three-component Mayo Clinic Score (MCS) comprising rectal bleeding, frequency of stool, and endoscopy.

Those patients who achieved an MCS score between 4 and 9 points with an endoscopic subscore of at least 2 and rectal bleeding (RB) subscore of at least 1 were included. Patients were divided into once-daily etrasimod 1 mg (52 patients), once-daily etrasimod 2 mg (50 patients) and placebo (54 patients) groups and treated over a 12-week period.

At 12 weeks, the least-squares mean difference for change in baseline in three-component MCS was 1.94 in the 1-mg etrasimod group and 2.49 in the 2-mg etrasimod group compared with placebo (1.50). Endoscopic improvement was greater in the 1-mg etrasimod (22.5%) and 2-mg (41.8%) groups compared with placebo (17.8%); endoscopic remission rates also improved in the 1-mg etrasimod (13.7%) and 2-mg (15.3%) groups compared with placebo (5.3%). Lymphocyte count circulation significantly decreased in the 1-mg etrasimod (37.2%) and 2-mg (57.3%) groups compared with the placebo group. With regard to rectal bleeding, the rectal bleeding subscore also decreased in the 1-mg etrasimod and 2-mg groups compared with placebo at 12 weeks from baseline.

The researchers noted no significant differences in adverse events among groups, with the placebo group showing a higher rate of major adverse events (11.1%) compared with the 1-mg etrasimod (5.8%) and 2-mg etrasimod (0%) groups.

“The OASIS trial results for etrasimod would support proceeding to a phase 3 program for this drug in patients with moderate to severe ulcerative colitis,” Dr. Sandborn concluded.

Dr. Sandborn reports consultancies, speaker bureau memberships, and research support from AbbVie, Biogen, Celgene, Ferring, Genentech, Gilead Sciences, Immune Pharmaceuticals, Janssen, Lilly, MedImmune, Novartis, Pfizer, Regeneron, Ritter Pharmaceuticals, Salix, Theradiag, UCB Pharma, and Vascular Biogenics, among others.

SOURCE: Sandborn WJ et al. ACG 2018. Presentation 11.

PHILADELPHIA – Use of etrasimod was associated with improved clinical and endoscopic results, and was generally safe and well tolerated compared with placebo in patients with moderate to severe ulcerative colitis, according to a recent award-winning presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

“Patients with moderate to severe ulcerative colitis receiving etrasimod 2 mg per day achieved statistically significant and clinically meaningful differences in all of the primary and secondary endpoints, and most exploratory endpoints were also significantly proved,” William J. Sandborn, MD, AGAF, FACG, professor of clinical medicine at the University of California, San Diego, stated in his presentation at the meeting. “A dose-response relationship was observed in virtually all of the measures of treatment efficacy.”

The abstract received the ACG Auxiliary Award (Member), which is given to ACG members each year with outstanding abstract submissions.

Dr. Sandborn and his colleagues enrolled 156 patients with ulcerative colitis (UC) into the OASIS study, a randomized, double-blind, parallel-group, phase 2 study of etrasimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, compared with placebo. Patients were aged 18-80 years, with moderate to severe UC as defined by a three-component Mayo Clinic Score (MCS) comprising rectal bleeding, frequency of stool, and endoscopy.

Those patients who achieved an MCS score between 4 and 9 points with an endoscopic subscore of at least 2 and rectal bleeding (RB) subscore of at least 1 were included. Patients were divided into once-daily etrasimod 1 mg (52 patients), once-daily etrasimod 2 mg (50 patients) and placebo (54 patients) groups and treated over a 12-week period.

At 12 weeks, the least-squares mean difference for change in baseline in three-component MCS was 1.94 in the 1-mg etrasimod group and 2.49 in the 2-mg etrasimod group compared with placebo (1.50). Endoscopic improvement was greater in the 1-mg etrasimod (22.5%) and 2-mg (41.8%) groups compared with placebo (17.8%); endoscopic remission rates also improved in the 1-mg etrasimod (13.7%) and 2-mg (15.3%) groups compared with placebo (5.3%). Lymphocyte count circulation significantly decreased in the 1-mg etrasimod (37.2%) and 2-mg (57.3%) groups compared with the placebo group. With regard to rectal bleeding, the rectal bleeding subscore also decreased in the 1-mg etrasimod and 2-mg groups compared with placebo at 12 weeks from baseline.

The researchers noted no significant differences in adverse events among groups, with the placebo group showing a higher rate of major adverse events (11.1%) compared with the 1-mg etrasimod (5.8%) and 2-mg etrasimod (0%) groups.

“The OASIS trial results for etrasimod would support proceeding to a phase 3 program for this drug in patients with moderate to severe ulcerative colitis,” Dr. Sandborn concluded.

Dr. Sandborn reports consultancies, speaker bureau memberships, and research support from AbbVie, Biogen, Celgene, Ferring, Genentech, Gilead Sciences, Immune Pharmaceuticals, Janssen, Lilly, MedImmune, Novartis, Pfizer, Regeneron, Ritter Pharmaceuticals, Salix, Theradiag, UCB Pharma, and Vascular Biogenics, among others.

SOURCE: Sandborn WJ et al. ACG 2018. Presentation 11.

PHILADELPHIA – Use of etrasimod was associated with improved clinical and endoscopic results, and was generally safe and well tolerated compared with placebo in patients with moderate to severe ulcerative colitis, according to a recent award-winning presentation at the annual meeting of the American College of Gastroenterology.

Jeff Craven/MDedge News

“Patients with moderate to severe ulcerative colitis receiving etrasimod 2 mg per day achieved statistically significant and clinically meaningful differences in all of the primary and secondary endpoints, and most exploratory endpoints were also significantly proved,” William J. Sandborn, MD, AGAF, FACG, professor of clinical medicine at the University of California, San Diego, stated in his presentation at the meeting. “A dose-response relationship was observed in virtually all of the measures of treatment efficacy.”

The abstract received the ACG Auxiliary Award (Member), which is given to ACG members each year with outstanding abstract submissions.

Dr. Sandborn and his colleagues enrolled 156 patients with ulcerative colitis (UC) into the OASIS study, a randomized, double-blind, parallel-group, phase 2 study of etrasimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, compared with placebo. Patients were aged 18-80 years, with moderate to severe UC as defined by a three-component Mayo Clinic Score (MCS) comprising rectal bleeding, frequency of stool, and endoscopy.

Those patients who achieved an MCS score between 4 and 9 points with an endoscopic subscore of at least 2 and rectal bleeding (RB) subscore of at least 1 were included. Patients were divided into once-daily etrasimod 1 mg (52 patients), once-daily etrasimod 2 mg (50 patients) and placebo (54 patients) groups and treated over a 12-week period.

At 12 weeks, the least-squares mean difference for change in baseline in three-component MCS was 1.94 in the 1-mg etrasimod group and 2.49 in the 2-mg etrasimod group compared with placebo (1.50). Endoscopic improvement was greater in the 1-mg etrasimod (22.5%) and 2-mg (41.8%) groups compared with placebo (17.8%); endoscopic remission rates also improved in the 1-mg etrasimod (13.7%) and 2-mg (15.3%) groups compared with placebo (5.3%). Lymphocyte count circulation significantly decreased in the 1-mg etrasimod (37.2%) and 2-mg (57.3%) groups compared with the placebo group. With regard to rectal bleeding, the rectal bleeding subscore also decreased in the 1-mg etrasimod and 2-mg groups compared with placebo at 12 weeks from baseline.

The researchers noted no significant differences in adverse events among groups, with the placebo group showing a higher rate of major adverse events (11.1%) compared with the 1-mg etrasimod (5.8%) and 2-mg etrasimod (0%) groups.

“The OASIS trial results for etrasimod would support proceeding to a phase 3 program for this drug in patients with moderate to severe ulcerative colitis,” Dr. Sandborn concluded.

Dr. Sandborn reports consultancies, speaker bureau memberships, and research support from AbbVie, Biogen, Celgene, Ferring, Genentech, Gilead Sciences, Immune Pharmaceuticals, Janssen, Lilly, MedImmune, Novartis, Pfizer, Regeneron, Ritter Pharmaceuticals, Salix, Theradiag, UCB Pharma, and Vascular Biogenics, among others.

SOURCE: Sandborn WJ et al. ACG 2018. Presentation 11.