The risk of cancer from N-nitrosodimethylamine (NDMA) contained in impure valsartan is real but very low, the Food and Drug Administration said in a July 27 statement.

The agency had announced a voluntary recall of valsartan from Major Pharmaceuticals, Solco Healthcare, and Teva Pharmaceuticals, as well as valsartan/hydrochlorothiazide from Solco and Teva, on July 13 after detection of NDMA, a semi-volatile organic compound. The manufacturer, Zhejiang Huahai Pharmaceuticals in Linhai, China, has since stopped distribution. Contamination probably is tied to a change in the manufacturing process.

NDMA has been linked to cancer in animal studies but at levels “much higher than the impurity levels in recalled valsartan batches.” Even so, the agency “wanted to put some context around the actual potential risk posed to patients who used versions of valsartan that may have contained high levels of NDMA,” the FDA said in its updated press release.

Based on records from the manufacturer, “some levels of the impurity may have been in the valsartan-containing products for as long as 4 years. FDA scientists estimate that if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for the full 4 years, there may be one additional case of cancer over the lifetimes of these 8,000 people,” the agency said.

“To put this in context, currently one out of every three people in the U.S. will experience cancer in their lifetime,” it said.

The FDA advised patients to check their prescriptions to see if they originate from one of the recalled batches, and to let their doctors and pharmacists know if they are.

To help, the FDA has posted a list of products included in the recall and a list of products not included in the recall.

Patients taking recalled valsartan should continue taking it until given a replacement. They should also follow the recall instructions provided by the specific companies, the FDA said.

[email protected]

The risk of cancer from N-nitrosodimethylamine (NDMA) contained in impure valsartan is real but very low, the Food and Drug Administration said in a July 27 statement.

The agency had announced a voluntary recall of valsartan from Major Pharmaceuticals, Solco Healthcare, and Teva Pharmaceuticals, as well as valsartan/hydrochlorothiazide from Solco and Teva, on July 13 after detection of NDMA, a semi-volatile organic compound. The manufacturer, Zhejiang Huahai Pharmaceuticals in Linhai, China, has since stopped distribution. Contamination probably is tied to a change in the manufacturing process.

NDMA has been linked to cancer in animal studies but at levels “much higher than the impurity levels in recalled valsartan batches.” Even so, the agency “wanted to put some context around the actual potential risk posed to patients who used versions of valsartan that may have contained high levels of NDMA,” the FDA said in its updated press release.

Based on records from the manufacturer, “some levels of the impurity may have been in the valsartan-containing products for as long as 4 years. FDA scientists estimate that if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for the full 4 years, there may be one additional case of cancer over the lifetimes of these 8,000 people,” the agency said.

“To put this in context, currently one out of every three people in the U.S. will experience cancer in their lifetime,” it said.

The FDA advised patients to check their prescriptions to see if they originate from one of the recalled batches, and to let their doctors and pharmacists know if they are.

To help, the FDA has posted a list of products included in the recall and a list of products not included in the recall.

Patients taking recalled valsartan should continue taking it until given a replacement. They should also follow the recall instructions provided by the specific companies, the FDA said.

[email protected]

The risk of cancer from N-nitrosodimethylamine (NDMA) contained in impure valsartan is real but very low, the Food and Drug Administration said in a July 27 statement.

The agency had announced a voluntary recall of valsartan from Major Pharmaceuticals, Solco Healthcare, and Teva Pharmaceuticals, as well as valsartan/hydrochlorothiazide from Solco and Teva, on July 13 after detection of NDMA, a semi-volatile organic compound. The manufacturer, Zhejiang Huahai Pharmaceuticals in Linhai, China, has since stopped distribution. Contamination probably is tied to a change in the manufacturing process.

NDMA has been linked to cancer in animal studies but at levels “much higher than the impurity levels in recalled valsartan batches.” Even so, the agency “wanted to put some context around the actual potential risk posed to patients who used versions of valsartan that may have contained high levels of NDMA,” the FDA said in its updated press release.

Based on records from the manufacturer, “some levels of the impurity may have been in the valsartan-containing products for as long as 4 years. FDA scientists estimate that if 8,000 people took the highest valsartan dose (320 mg) from the recalled batches daily for the full 4 years, there may be one additional case of cancer over the lifetimes of these 8,000 people,” the agency said.

“To put this in context, currently one out of every three people in the U.S. will experience cancer in their lifetime,” it said.

The FDA advised patients to check their prescriptions to see if they originate from one of the recalled batches, and to let their doctors and pharmacists know if they are.

To help, the FDA has posted a list of products included in the recall and a list of products not included in the recall.

Patients taking recalled valsartan should continue taking it until given a replacement. They should also follow the recall instructions provided by the specific companies, the FDA said.

[email protected]

PARIS – The Synergy bioabsorbable polymer everolimus-eluting stent performed equally well for treatment of acute MI, compared with other newer-generation drug-eluting stents, through 2 years of follow-up in a massive observational study of all patients undergoing percutaneous coronary intervention in Sweden during a recent multiyear period.

 

Bruce Jancin/MDedge News

This report from the prospective Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was undertaken because, even though the Synergy stent has demonstrated outstanding clinical results in randomized trials and observational studies, the stent’s performance specifically in the setting of acute MI had not previously been investigated, Sergio Buccheri, MD, noted at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

SCAAR, which documents every PCI performed in Sweden, provided the capability to fill that important knowledge gap in an unselected real-world population of acute MI patients. Dr. Buccheri, of Uppsala (Sweden) University, reported on 36,292 consecutive patients who underwent PCI with a newer-generation drug-eluting stent (DES) in Sweden from March 2013 to September 2016. Forty percent of them had ST-elevation MI. The Synergy stent was used in 4,889 patients. Among the most commonly used newer DES in the other 31,000-plus patients were the Xience Xpedition, the Resolute Integrity and Resolute Onyx, the Orsiro, BioMatrix, and Promus Element Plus and Promus Premier.

The coprimary endpoints in this analysis were the rates of definite stent thrombosis and clinically relevant restenosis at 2 years of follow-up. Stent thrombosis occurred in 0.69% of the Synergy patients and 0.81% of those who received other newer-generation DES, a nonsignificant difference. Similarly, no significant difference was found in the rate of clinically relevant restenosis: 1.48% and 1.25%, respectively.

“The rates of stent thrombosis and restenosis were reassuringly low with both Synergy and other newer-DES devices,” Dr. Buccheri noted. “These findings may be useful to support a more informed and evidence-based stent selection process in daily clinical practice.”

The key secondary outcomes were all-cause mortality and recurrent MI. Again, there were no significant between-group differences. The cumulative all-cause mortality at 2 years was 10.1% in the Synergy group and 9.1% in the others. Recurrent MI occurred in 6.49% of the Synergy group and 6.32% with other DES.

Patients who received the Synergy stent were on average older, had a higher burden of cardiovascular risk factors, and presented more often with left main, triple-vessel disease or vein graft lesions. For that reason, Dr. Buccheri and his coinvestigators developed a propensity score using an array of covariates to adjust for these differences. Plugging those scores into multivariate Cox regression models, there remained no significant differences between the two groups in the adjusted risk of any of the endpoints.

Operators were advised to use dual antiplatelet therapy for 12 months in all patients. However, SCAAR does not include data on adherence to DAPT, which is a study limitation, Dr. Buccheri noted.

The Synergy stent is made up of a thin strut chromium-platinum platform with a bioabsorbable polymer that releases everolimus. The polymer is completely reabsorbed within 4 months, leaving behind a bare metal stent. In animal models, this has been associated with lower levels of inflammation, compared with permanent polymer DES. And inflammation is thought to be one of the main mechanisms underlying stent failure in the late and very late phases after PCI.

The discussion panel was clearly impressed with – and envious of – the sheer size of the SCAAR study population. As one panelist noted, real-life data of this magnitude can really only be obtained in Sweden. Another panelist confessed: “We’re shy of presenting our own studies when we see these numbers.”

Simultaneously with Dr. Buccheri’s presentation, the SCAAR report was published online (EuroIntervention. 2018 May 24. pii: EIJ-D-18-00392. doi: 10.4244/EIJ-D-18-00392).

SCAAR is funded solely by the Swedish government. This study was supported by a grant from Boston Scientific. Dr. Buccheri reported having no financial conflicts of interest.

[email protected]

PARIS – The Synergy bioabsorbable polymer everolimus-eluting stent performed equally well for treatment of acute MI, compared with other newer-generation drug-eluting stents, through 2 years of follow-up in a massive observational study of all patients undergoing percutaneous coronary intervention in Sweden during a recent multiyear period.

 

Bruce Jancin/MDedge News

This report from the prospective Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was undertaken because, even though the Synergy stent has demonstrated outstanding clinical results in randomized trials and observational studies, the stent’s performance specifically in the setting of acute MI had not previously been investigated, Sergio Buccheri, MD, noted at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

SCAAR, which documents every PCI performed in Sweden, provided the capability to fill that important knowledge gap in an unselected real-world population of acute MI patients. Dr. Buccheri, of Uppsala (Sweden) University, reported on 36,292 consecutive patients who underwent PCI with a newer-generation drug-eluting stent (DES) in Sweden from March 2013 to September 2016. Forty percent of them had ST-elevation MI. The Synergy stent was used in 4,889 patients. Among the most commonly used newer DES in the other 31,000-plus patients were the Xience Xpedition, the Resolute Integrity and Resolute Onyx, the Orsiro, BioMatrix, and Promus Element Plus and Promus Premier.

The coprimary endpoints in this analysis were the rates of definite stent thrombosis and clinically relevant restenosis at 2 years of follow-up. Stent thrombosis occurred in 0.69% of the Synergy patients and 0.81% of those who received other newer-generation DES, a nonsignificant difference. Similarly, no significant difference was found in the rate of clinically relevant restenosis: 1.48% and 1.25%, respectively.

“The rates of stent thrombosis and restenosis were reassuringly low with both Synergy and other newer-DES devices,” Dr. Buccheri noted. “These findings may be useful to support a more informed and evidence-based stent selection process in daily clinical practice.”

The key secondary outcomes were all-cause mortality and recurrent MI. Again, there were no significant between-group differences. The cumulative all-cause mortality at 2 years was 10.1% in the Synergy group and 9.1% in the others. Recurrent MI occurred in 6.49% of the Synergy group and 6.32% with other DES.

Patients who received the Synergy stent were on average older, had a higher burden of cardiovascular risk factors, and presented more often with left main, triple-vessel disease or vein graft lesions. For that reason, Dr. Buccheri and his coinvestigators developed a propensity score using an array of covariates to adjust for these differences. Plugging those scores into multivariate Cox regression models, there remained no significant differences between the two groups in the adjusted risk of any of the endpoints.

Operators were advised to use dual antiplatelet therapy for 12 months in all patients. However, SCAAR does not include data on adherence to DAPT, which is a study limitation, Dr. Buccheri noted.

The Synergy stent is made up of a thin strut chromium-platinum platform with a bioabsorbable polymer that releases everolimus. The polymer is completely reabsorbed within 4 months, leaving behind a bare metal stent. In animal models, this has been associated with lower levels of inflammation, compared with permanent polymer DES. And inflammation is thought to be one of the main mechanisms underlying stent failure in the late and very late phases after PCI.

The discussion panel was clearly impressed with – and envious of – the sheer size of the SCAAR study population. As one panelist noted, real-life data of this magnitude can really only be obtained in Sweden. Another panelist confessed: “We’re shy of presenting our own studies when we see these numbers.”

Simultaneously with Dr. Buccheri’s presentation, the SCAAR report was published online (EuroIntervention. 2018 May 24. pii: EIJ-D-18-00392. doi: 10.4244/EIJ-D-18-00392).

SCAAR is funded solely by the Swedish government. This study was supported by a grant from Boston Scientific. Dr. Buccheri reported having no financial conflicts of interest.

[email protected]

PARIS – The Synergy bioabsorbable polymer everolimus-eluting stent performed equally well for treatment of acute MI, compared with other newer-generation drug-eluting stents, through 2 years of follow-up in a massive observational study of all patients undergoing percutaneous coronary intervention in Sweden during a recent multiyear period.

 

Bruce Jancin/MDedge News

This report from the prospective Swedish Coronary Angiography and Angioplasty Registry (SCAAR) was undertaken because, even though the Synergy stent has demonstrated outstanding clinical results in randomized trials and observational studies, the stent’s performance specifically in the setting of acute MI had not previously been investigated, Sergio Buccheri, MD, noted at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions.

SCAAR, which documents every PCI performed in Sweden, provided the capability to fill that important knowledge gap in an unselected real-world population of acute MI patients. Dr. Buccheri, of Uppsala (Sweden) University, reported on 36,292 consecutive patients who underwent PCI with a newer-generation drug-eluting stent (DES) in Sweden from March 2013 to September 2016. Forty percent of them had ST-elevation MI. The Synergy stent was used in 4,889 patients. Among the most commonly used newer DES in the other 31,000-plus patients were the Xience Xpedition, the Resolute Integrity and Resolute Onyx, the Orsiro, BioMatrix, and Promus Element Plus and Promus Premier.

The coprimary endpoints in this analysis were the rates of definite stent thrombosis and clinically relevant restenosis at 2 years of follow-up. Stent thrombosis occurred in 0.69% of the Synergy patients and 0.81% of those who received other newer-generation DES, a nonsignificant difference. Similarly, no significant difference was found in the rate of clinically relevant restenosis: 1.48% and 1.25%, respectively.

“The rates of stent thrombosis and restenosis were reassuringly low with both Synergy and other newer-DES devices,” Dr. Buccheri noted. “These findings may be useful to support a more informed and evidence-based stent selection process in daily clinical practice.”

The key secondary outcomes were all-cause mortality and recurrent MI. Again, there were no significant between-group differences. The cumulative all-cause mortality at 2 years was 10.1% in the Synergy group and 9.1% in the others. Recurrent MI occurred in 6.49% of the Synergy group and 6.32% with other DES.

Patients who received the Synergy stent were on average older, had a higher burden of cardiovascular risk factors, and presented more often with left main, triple-vessel disease or vein graft lesions. For that reason, Dr. Buccheri and his coinvestigators developed a propensity score using an array of covariates to adjust for these differences. Plugging those scores into multivariate Cox regression models, there remained no significant differences between the two groups in the adjusted risk of any of the endpoints.

Operators were advised to use dual antiplatelet therapy for 12 months in all patients. However, SCAAR does not include data on adherence to DAPT, which is a study limitation, Dr. Buccheri noted.

The Synergy stent is made up of a thin strut chromium-platinum platform with a bioabsorbable polymer that releases everolimus. The polymer is completely reabsorbed within 4 months, leaving behind a bare metal stent. In animal models, this has been associated with lower levels of inflammation, compared with permanent polymer DES. And inflammation is thought to be one of the main mechanisms underlying stent failure in the late and very late phases after PCI.

The discussion panel was clearly impressed with – and envious of – the sheer size of the SCAAR study population. As one panelist noted, real-life data of this magnitude can really only be obtained in Sweden. Another panelist confessed: “We’re shy of presenting our own studies when we see these numbers.”

Simultaneously with Dr. Buccheri’s presentation, the SCAAR report was published online (EuroIntervention. 2018 May 24. pii: EIJ-D-18-00392. doi: 10.4244/EIJ-D-18-00392).

SCAAR is funded solely by the Swedish government. This study was supported by a grant from Boston Scientific. Dr. Buccheri reported having no financial conflicts of interest.

[email protected]

Photo by Chad McNeeley

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending orphan drug designation for OMS721 as a treatment for high-risk hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).

OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.

The COMP’s positive opinion of OMS721 for HSCT-TMA is expected to be adopted by the European Commission in August.

Orphan drug designation in Europe is available to companies developing products intended to treat a life-threatening or chronically debilitating condition that affects fewer than 5 in 10,000 people in the European Union (EU).

This designation allows for financial and regulatory incentives that include 10 years of marketing exclusivity in the EU after product approval, reduced EMA advisory, inspection and filing fees pre- and post-approval, and guaranteed access to centralized marketing authorization valid in all EU member states as well as in European Economic Area countries (ie, Iceland, Liechtenstein, and Norway).

Phase 2 trial

OMS721 is currently under evaluation in a phase 2 trial (NCT02222545). Omeros Corporation, the company developing OMS721, released some results from this study in February.

Results were reported for 18 adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post-transplant. The patients received weekly OMS721 treatments for 4 to 8 weeks at the discretion of the investigator.

These patients had a significantly longer median overall survival than historical controls—347 days and 21 days, respectively (P<0.0001).

Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.

The mean platelet count increased from 18,100 x 10⁶/mL at baseline to 52,300 x 10⁶/mL (P=0.017). The mean LDH decreased from 591 U/L to 250 U/L (P<0.001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P=0.003).

Mean creatinine remained stable—at approximately 120 μmol/L—but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. These conditions included graft-versus-host disease, cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.

The most commonly reported adverse events in this trial were diarrhea and neutropenia.

Four deaths occurred. One of these—due to acute renal and respiratory failure—was considered possibly related to OMS721.

The other deaths were due to progression of acute myeloid leukemia (n=1) and neutropenic sepsis (n=2).

Photo by Chad McNeeley

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending orphan drug designation for OMS721 as a treatment for high-risk hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).

OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.

The COMP’s positive opinion of OMS721 for HSCT-TMA is expected to be adopted by the European Commission in August.

Orphan drug designation in Europe is available to companies developing products intended to treat a life-threatening or chronically debilitating condition that affects fewer than 5 in 10,000 people in the European Union (EU).

This designation allows for financial and regulatory incentives that include 10 years of marketing exclusivity in the EU after product approval, reduced EMA advisory, inspection and filing fees pre- and post-approval, and guaranteed access to centralized marketing authorization valid in all EU member states as well as in European Economic Area countries (ie, Iceland, Liechtenstein, and Norway).

Phase 2 trial

OMS721 is currently under evaluation in a phase 2 trial (NCT02222545). Omeros Corporation, the company developing OMS721, released some results from this study in February.

Results were reported for 18 adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post-transplant. The patients received weekly OMS721 treatments for 4 to 8 weeks at the discretion of the investigator.

These patients had a significantly longer median overall survival than historical controls—347 days and 21 days, respectively (P<0.0001).

Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.

The mean platelet count increased from 18,100 x 10⁶/mL at baseline to 52,300 x 10⁶/mL (P=0.017). The mean LDH decreased from 591 U/L to 250 U/L (P<0.001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P=0.003).

Mean creatinine remained stable—at approximately 120 μmol/L—but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. These conditions included graft-versus-host disease, cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.

The most commonly reported adverse events in this trial were diarrhea and neutropenia.

Four deaths occurred. One of these—due to acute renal and respiratory failure—was considered possibly related to OMS721.

The other deaths were due to progression of acute myeloid leukemia (n=1) and neutropenic sepsis (n=2).

Photo by Chad McNeeley

The European Medicines Agency’s (EMA’s) Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending orphan drug designation for OMS721 as a treatment for high-risk hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA).

OMS721 is a monoclonal antibody targeting MASP-2, the effector enzyme of the lectin pathway of the complement system.

The COMP’s positive opinion of OMS721 for HSCT-TMA is expected to be adopted by the European Commission in August.

Orphan drug designation in Europe is available to companies developing products intended to treat a life-threatening or chronically debilitating condition that affects fewer than 5 in 10,000 people in the European Union (EU).

This designation allows for financial and regulatory incentives that include 10 years of marketing exclusivity in the EU after product approval, reduced EMA advisory, inspection and filing fees pre- and post-approval, and guaranteed access to centralized marketing authorization valid in all EU member states as well as in European Economic Area countries (ie, Iceland, Liechtenstein, and Norway).

Phase 2 trial

OMS721 is currently under evaluation in a phase 2 trial (NCT02222545). Omeros Corporation, the company developing OMS721, released some results from this study in February.

Results were reported for 18 adults with HSCT-TMA persisting for at least 2 weeks following immunosuppressive regimen modification or more than 30 days post-transplant. The patients received weekly OMS721 treatments for 4 to 8 weeks at the discretion of the investigator.

These patients had a significantly longer median overall survival than historical controls—347 days and 21 days, respectively (P<0.0001).

Omeros also reported that markers of TMA activity significantly improved following OMS721 treatment.

The mean platelet count increased from 18,100 x 10⁶/mL at baseline to 52,300 x 10⁶/mL (P=0.017). The mean LDH decreased from 591 U/L to 250 U/L (P<0.001). And the mean haptoglobin increased from 8 mg/dL to 141 mg/dL (P=0.003).

Mean creatinine remained stable—at approximately 120 μmol/L—but a majority of patients had co-existing conditions for which they were receiving nephrotoxic medications. These conditions included graft-versus-host disease, cytomegalovirus and human herpes virus 6 infections, prior sepsis, diffuse alveolar hemorrhage, and residual underlying malignancies.

The most commonly reported adverse events in this trial were diarrhea and neutropenia.

Four deaths occurred. One of these—due to acute renal and respiratory failure—was considered possibly related to OMS721.

The other deaths were due to progression of acute myeloid leukemia (n=1) and neutropenic sepsis (n=2).

 

SAN FRANCISCO – After a lengthy drought in the development of major new headache medications, it was finally raining successful phase 3 clinical trials for novel drugs at the annual meeting of the American Headache Society.

Bruce Jancin/MDedge News

From the podium, as a prelude to presenting one of many positive trials, Richard B. Lipton, MD, was moved to paraphrase Charles Dickens: “ ‘It was the best of times’ ... and these are truly the best of times,” the neurologist observed.

“This morning we’ve heard about seven new molecular entities that are effective in the acute and/or preventive treatment of migraine, a couple of novel ways of delivering older drugs, and some interesting comparative effectiveness research. I have this compulsion to say over and over again – because I also work in Alzheimer’s disease – it just isn’t like this in other fields. This is truly a remarkable time in our field,” observed Dr. Lipton, professor and vice chair of the department of neurology at Albert Einstein College of Medicine in New York.

In addition to new studies of erenumab-aooe, which has been approved as Aimovig, the first-in-class calcitonin gene-related peptide (CGRP) inhibitor for the preventive treatment of migraine, the headache meeting also featured new positive phase 3 results for three other anti-CGRP monoclonal antibodies – galcanezumab, fremanezumab, and eptinezumab – as migraine-preventive therapy, with galcanezumab also demonstrating efficacy in episodic cluster headache; the oral small-molecule CGRP antagonists rimegepant and ubrogepant for acute treatment of migraine attacks; and the selective serotonin 5-HT 1F agonist lasmiditan, also for acute treatment of migraine.

Although the mechanisms of action and therapeutic purposes of the novel agents differ, they share in common what appears to be far better safety and tolerability than the current market leaders, topiramate (Topamax) for migraine prevention and the triptans for acute treatment.

Here are study highlights for the three potential new treatments for acute migraine attacks:

Rimegepant

Dr. Lipton presented the results of two virtually identical phase-3, double-blind, randomized trials in which a total of 2,162 patients with episodic migraine self-administered a 75-mg oral tablet of rimegepant or placebo to treat a single migraine attack when their headache pain reached moderate or severe intensity. The clinical trials, which lacked the customary snazzy acronyms, were simply called Study 301 and Study 302.

The two co-primary endpoints now required by the Food and Drug Administration for candidate agents for acute treatment of migraine attacks are freedom from pain and absence of the most bothersome symptom, both as assessed 2 hours post dose. The oral CGRP receptor antagonist met both endpoints, as well as key secondary endpoints.

In Study 302, for example, the pain-free rate 2 hours post dose was 19.6% in the rimegepant group, significantly higher than the 12% rate in placebo-treated controls. The rate of freedom from the most bothersome symptom, which was photophobia in the majority of patients, was 37.6% in the rimegepant group and 25.2% with placebo.

Dr. Lipton characterized the benefits seen with a single dose of rimegepant as “broad and clinically important.”

“The majority of patients achieved pain relief, durability of benefit at 24 and 48 hours, lower use of rescue medications, and a greater proportion of patients achieved normal function,” the neurologist reported.

The safety and tolerability profiles of rimegepant mirrored those of placebo, he added.

 

Ubrogepant

Dr. Lipton also presented the results of ACHIEVE II, a multicenter, double-blind, phase 3, placebo-controlled study of the oral CGRP receptor antagonist ubrogepant at 25 or 50 mg versus placebo in 1,355 patients with episodic migraine. Like rimegepant, it met both FDA-required primary endpoints. The pain freedom rate 2 hours post dose was 20.7% with ubrogepant at 25 mg, 21.8% with 50 mg, and 14.3% with placebo. The most bothersome symptom was gone at 2 hours in 34.1% of patients who received the CGRP receptor antagonist at 25 mg, 38.9% of those who got the 50-mg dose, and 27.4% of controls.

David W. Dodick, MD, explained the rationale for CGRP inhibition: CGRP and its receptors are highly expressed in pain-sensitive trigeminal sensory neurons, which innervate the dura and meningeal blood vessels. During the headache phase of migraine, the peptide is released in excess, making CGRP a key player in the pathophysiology of migraine.

Dr. Dodick presented an update focused on secondary endpoints in the phase 3, double-blind ACHIEVE I trial, whose positive co-primary outcomes have previously been reported. The analysis included 1,327 episodic migraine patients who were randomized to ubrogepant at 50 or 100 mg or placebo. Among the notable secondary outcomes was the clinically important rate of pain relief at 2 hours: 61% in both ubrogepant groups, significantly better than the 49% rate with placebo. Also, in terms of pain freedom, the 2-hour rate underestimated the true efficacy patients would experience in clinical practice: the maximum pain freedom rate occurred at 3 hours and was sustained to 8 hours post dose.

At the time study participants took their pill, only 30% indicated they were capable of functioning normally. Two hours later, this was still the case in 29.8% of placebo-treated controls, as compared with 40.6% on ubrogepant at 50 mg and 42.9% who took 100 mg of the drug. The proportion of patients who said they were satisfied or extremely satisfied with their treatment at the 2-hour mark was 24.1% in the placebo arm and 36.3% and 35.8% in the lower- and higher-dose ubrogepant arms, reported Dr. Dodick, professor of neurology at the Mayo Clinic in Scottsdale, Ariz.
 

Lasmiditan

Sheena K. Aurora, MD, presented the results of SAMURAI and SPARTAN, two randomized, double-blind, phase 3 clinical trials comparing lasmiditan versus placebo for the treatment of acute migraine in a collective 3,701 patients with longstanding episodic migraine, one-third of whom had a history of aura.

Bruce Jancin/MDedge News

Lasmiditan is a novel oral serotonin receptor agonist that penetrates the CNS and selectively targets the 5-HT 1F receptor. The drug doesn’t cause the vasoconstrictive effects that make triptans, which target 5-HT 1B/1D receptors, contraindicated in patients with cardiovascular disease.

Indeed, SPARTAN included patients with known cardiovascular disease. SAMURAI did not; however, migraine is now recognized as an independent cardiovascular risk factor, and 80% of SAMURAI participants had one additional standard cardiovascular risk factor, such as diabetes, smoking, or hypertension.

SAMURAI randomized patients to lasmiditan at 100 or 200 mg or placebo to be taken within 4 hours of migraine onset, when the pain was of at least moderate severity. SPARTAN randomized patients to lasmiditan at 50, 100, or 200 mg or placebo.

A dose-response effect was noted. At 2 hours post dose of lasmiditan at 200 mg, 32.2% of patients in SAMURAI and 38.8% in SPARTAN were pain-free, compared with 15.3% and 21.3% on placebo, respectively. At the top dose of lasmiditan, 40.7% of patients in SAMURAI were free of their most bothersome baseline symptom, as were 48.7% in SPARTAN, with placebo response rates of 29.5% and 33.5%, respectively, for this endpoint. A significant separation from placebo was noted in 1 hour for the pain freedom endpoint, and in about 30 minutes for freedom from the most bothersome symptom, reported Dr. Aurora of Eli Lilly, which sponsored the trials.

Lasmiditan at 50 and 100 mg also significantly outperformed placebo for the co-primary endpoints.

As in the phase 3 trials of the two investigational oral CGRP antagonists, a secondary endpoint in SPARTAN and SAMURAI was pain relief at 2 hours, a lower bar than pain freedom. The rates in the lasmiditan 200 mg arms were 60%-65%, compared with about 40% with placebo.

Treatment-emergent adverse event rates were 11%-15% with placebo and in the 40% range for lasmiditan. Because the drug penetrates the CNS, centrally acting side effects were an issue. Dizziness was the most common, followed by paresthesia, somnolence, then fatigue. The dizziness was dose dependent: In SPARTAN, the complaint was noted in 2.5% of placebo-treated controls, 25.4% of patients on 50 mg of lasmiditan, 36.1% with 100 mg, and 39% at 200 mg.

Chest tightness, a common side effect with triptans, did not occur.

A large multicenter, open-label safety assessment study, called GLADIATOR, is ongoing.
 

 

Triptans, what have you done for me lately?

A recurring theme at the headache meeting was the vast unmet need for better treatments for acute migraine attacks.

“You all know very well that triptans have been the most widely prescribed acute treatments for migraine in North America now for decades, but there are people with unmet treatment needs,” Dr. Lipton said. “Depending on how you define it, perhaps 34% of patients do not respond, 30%-40% have attack recurrence, and 3.5 million people have absolute or relative contraindications to triptans among the 40 million people who have migraine in the United States.”

Bruce Jancin/MDedge News

This was underscored by an analysis presented by Aftab Alam, MD, from the MAST (Migraine in America Symptoms and Treatment) study, a nationally representative cohort of 15,133 American adults with migraine and a mean monthly headache frequency of 3.3 days per month. Even though triptans are considered the gold standard acute migraine therapy, only 37% of participants in the detailed 30- to 40-minute survey had ever used a triptan, and just 15.9% of the overall study population were current users. Current triptan users averaged 7.3 headache days per month. A total of 85% of current users took oral formulations, 17% used nasal spray, and 8% utilized injectable triptans.

Among ever-users of triptans, 56.7% had discontinued them. The No.1 reason cited was lack of efficacy, named by 38% of those who stopped oral agents, 40% with the nasal spray, and 26% who discontinued injectables.

The second most common reason for triptan discontinuation was side effects, the most common of which was dizziness, followed by nausea and fatigue. Lack of insurance coverage was cited by only 6% of patients as a reason they discontinued triptans.

These MAST results suggest “there is a lot of unmet need in this area,” commented Dr. Alam, director of clinical development and medical affairs at Dr. Reddy’s Laboratories, Princeton, N.J. The MAST study was funded by Promius Pharma, a subsidiary of Dr. Reddy’s Laboratories.

Dr. Lipton reported serving as a consultant to more than a dozen pharmaceutical and medical device companies and holding stock options for Biohaven Pharmaceuticals, which is developing rimegepant.

Dr. Dodick reported serving as a consultant to Allergan, which sponsored the ubrogepant studies, as well as numerous other companies.

[email protected]

SOURCES: AHS Annual Meeting Abstracts. Alam A et al. Headache. 2018;58(Suppl 2):68. Abstract OR11; Wietecha L et al. Headache. 2018;58(Suppl 2):73. Abstract IOR02; Dodick D et al. AHS 2018 Abstract IOR01LB; Lipton R et al. AHS 2018 Abstract IOR02LB.

 

SAN FRANCISCO – After a lengthy drought in the development of major new headache medications, it was finally raining successful phase 3 clinical trials for novel drugs at the annual meeting of the American Headache Society.

Bruce Jancin/MDedge News

From the podium, as a prelude to presenting one of many positive trials, Richard B. Lipton, MD, was moved to paraphrase Charles Dickens: “ ‘It was the best of times’ ... and these are truly the best of times,” the neurologist observed.

“This morning we’ve heard about seven new molecular entities that are effective in the acute and/or preventive treatment of migraine, a couple of novel ways of delivering older drugs, and some interesting comparative effectiveness research. I have this compulsion to say over and over again – because I also work in Alzheimer’s disease – it just isn’t like this in other fields. This is truly a remarkable time in our field,” observed Dr. Lipton, professor and vice chair of the department of neurology at Albert Einstein College of Medicine in New York.

In addition to new studies of erenumab-aooe, which has been approved as Aimovig, the first-in-class calcitonin gene-related peptide (CGRP) inhibitor for the preventive treatment of migraine, the headache meeting also featured new positive phase 3 results for three other anti-CGRP monoclonal antibodies – galcanezumab, fremanezumab, and eptinezumab – as migraine-preventive therapy, with galcanezumab also demonstrating efficacy in episodic cluster headache; the oral small-molecule CGRP antagonists rimegepant and ubrogepant for acute treatment of migraine attacks; and the selective serotonin 5-HT 1F agonist lasmiditan, also for acute treatment of migraine.

Although the mechanisms of action and therapeutic purposes of the novel agents differ, they share in common what appears to be far better safety and tolerability than the current market leaders, topiramate (Topamax) for migraine prevention and the triptans for acute treatment.

Here are study highlights for the three potential new treatments for acute migraine attacks:

Rimegepant

Dr. Lipton presented the results of two virtually identical phase-3, double-blind, randomized trials in which a total of 2,162 patients with episodic migraine self-administered a 75-mg oral tablet of rimegepant or placebo to treat a single migraine attack when their headache pain reached moderate or severe intensity. The clinical trials, which lacked the customary snazzy acronyms, were simply called Study 301 and Study 302.

The two co-primary endpoints now required by the Food and Drug Administration for candidate agents for acute treatment of migraine attacks are freedom from pain and absence of the most bothersome symptom, both as assessed 2 hours post dose. The oral CGRP receptor antagonist met both endpoints, as well as key secondary endpoints.

In Study 302, for example, the pain-free rate 2 hours post dose was 19.6% in the rimegepant group, significantly higher than the 12% rate in placebo-treated controls. The rate of freedom from the most bothersome symptom, which was photophobia in the majority of patients, was 37.6% in the rimegepant group and 25.2% with placebo.

Dr. Lipton characterized the benefits seen with a single dose of rimegepant as “broad and clinically important.”

“The majority of patients achieved pain relief, durability of benefit at 24 and 48 hours, lower use of rescue medications, and a greater proportion of patients achieved normal function,” the neurologist reported.

The safety and tolerability profiles of rimegepant mirrored those of placebo, he added.

 

Ubrogepant

Dr. Lipton also presented the results of ACHIEVE II, a multicenter, double-blind, phase 3, placebo-controlled study of the oral CGRP receptor antagonist ubrogepant at 25 or 50 mg versus placebo in 1,355 patients with episodic migraine. Like rimegepant, it met both FDA-required primary endpoints. The pain freedom rate 2 hours post dose was 20.7% with ubrogepant at 25 mg, 21.8% with 50 mg, and 14.3% with placebo. The most bothersome symptom was gone at 2 hours in 34.1% of patients who received the CGRP receptor antagonist at 25 mg, 38.9% of those who got the 50-mg dose, and 27.4% of controls.

David W. Dodick, MD, explained the rationale for CGRP inhibition: CGRP and its receptors are highly expressed in pain-sensitive trigeminal sensory neurons, which innervate the dura and meningeal blood vessels. During the headache phase of migraine, the peptide is released in excess, making CGRP a key player in the pathophysiology of migraine.

Dr. Dodick presented an update focused on secondary endpoints in the phase 3, double-blind ACHIEVE I trial, whose positive co-primary outcomes have previously been reported. The analysis included 1,327 episodic migraine patients who were randomized to ubrogepant at 50 or 100 mg or placebo. Among the notable secondary outcomes was the clinically important rate of pain relief at 2 hours: 61% in both ubrogepant groups, significantly better than the 49% rate with placebo. Also, in terms of pain freedom, the 2-hour rate underestimated the true efficacy patients would experience in clinical practice: the maximum pain freedom rate occurred at 3 hours and was sustained to 8 hours post dose.

At the time study participants took their pill, only 30% indicated they were capable of functioning normally. Two hours later, this was still the case in 29.8% of placebo-treated controls, as compared with 40.6% on ubrogepant at 50 mg and 42.9% who took 100 mg of the drug. The proportion of patients who said they were satisfied or extremely satisfied with their treatment at the 2-hour mark was 24.1% in the placebo arm and 36.3% and 35.8% in the lower- and higher-dose ubrogepant arms, reported Dr. Dodick, professor of neurology at the Mayo Clinic in Scottsdale, Ariz.
 

Lasmiditan

Sheena K. Aurora, MD, presented the results of SAMURAI and SPARTAN, two randomized, double-blind, phase 3 clinical trials comparing lasmiditan versus placebo for the treatment of acute migraine in a collective 3,701 patients with longstanding episodic migraine, one-third of whom had a history of aura.

Bruce Jancin/MDedge News

Lasmiditan is a novel oral serotonin receptor agonist that penetrates the CNS and selectively targets the 5-HT 1F receptor. The drug doesn’t cause the vasoconstrictive effects that make triptans, which target 5-HT 1B/1D receptors, contraindicated in patients with cardiovascular disease.

Indeed, SPARTAN included patients with known cardiovascular disease. SAMURAI did not; however, migraine is now recognized as an independent cardiovascular risk factor, and 80% of SAMURAI participants had one additional standard cardiovascular risk factor, such as diabetes, smoking, or hypertension.

SAMURAI randomized patients to lasmiditan at 100 or 200 mg or placebo to be taken within 4 hours of migraine onset, when the pain was of at least moderate severity. SPARTAN randomized patients to lasmiditan at 50, 100, or 200 mg or placebo.

A dose-response effect was noted. At 2 hours post dose of lasmiditan at 200 mg, 32.2% of patients in SAMURAI and 38.8% in SPARTAN were pain-free, compared with 15.3% and 21.3% on placebo, respectively. At the top dose of lasmiditan, 40.7% of patients in SAMURAI were free of their most bothersome baseline symptom, as were 48.7% in SPARTAN, with placebo response rates of 29.5% and 33.5%, respectively, for this endpoint. A significant separation from placebo was noted in 1 hour for the pain freedom endpoint, and in about 30 minutes for freedom from the most bothersome symptom, reported Dr. Aurora of Eli Lilly, which sponsored the trials.

Lasmiditan at 50 and 100 mg also significantly outperformed placebo for the co-primary endpoints.

As in the phase 3 trials of the two investigational oral CGRP antagonists, a secondary endpoint in SPARTAN and SAMURAI was pain relief at 2 hours, a lower bar than pain freedom. The rates in the lasmiditan 200 mg arms were 60%-65%, compared with about 40% with placebo.

Treatment-emergent adverse event rates were 11%-15% with placebo and in the 40% range for lasmiditan. Because the drug penetrates the CNS, centrally acting side effects were an issue. Dizziness was the most common, followed by paresthesia, somnolence, then fatigue. The dizziness was dose dependent: In SPARTAN, the complaint was noted in 2.5% of placebo-treated controls, 25.4% of patients on 50 mg of lasmiditan, 36.1% with 100 mg, and 39% at 200 mg.

Chest tightness, a common side effect with triptans, did not occur.

A large multicenter, open-label safety assessment study, called GLADIATOR, is ongoing.
 

 

Triptans, what have you done for me lately?

A recurring theme at the headache meeting was the vast unmet need for better treatments for acute migraine attacks.

“You all know very well that triptans have been the most widely prescribed acute treatments for migraine in North America now for decades, but there are people with unmet treatment needs,” Dr. Lipton said. “Depending on how you define it, perhaps 34% of patients do not respond, 30%-40% have attack recurrence, and 3.5 million people have absolute or relative contraindications to triptans among the 40 million people who have migraine in the United States.”

Bruce Jancin/MDedge News

This was underscored by an analysis presented by Aftab Alam, MD, from the MAST (Migraine in America Symptoms and Treatment) study, a nationally representative cohort of 15,133 American adults with migraine and a mean monthly headache frequency of 3.3 days per month. Even though triptans are considered the gold standard acute migraine therapy, only 37% of participants in the detailed 30- to 40-minute survey had ever used a triptan, and just 15.9% of the overall study population were current users. Current triptan users averaged 7.3 headache days per month. A total of 85% of current users took oral formulations, 17% used nasal spray, and 8% utilized injectable triptans.

Among ever-users of triptans, 56.7% had discontinued them. The No.1 reason cited was lack of efficacy, named by 38% of those who stopped oral agents, 40% with the nasal spray, and 26% who discontinued injectables.

The second most common reason for triptan discontinuation was side effects, the most common of which was dizziness, followed by nausea and fatigue. Lack of insurance coverage was cited by only 6% of patients as a reason they discontinued triptans.

These MAST results suggest “there is a lot of unmet need in this area,” commented Dr. Alam, director of clinical development and medical affairs at Dr. Reddy’s Laboratories, Princeton, N.J. The MAST study was funded by Promius Pharma, a subsidiary of Dr. Reddy’s Laboratories.

Dr. Lipton reported serving as a consultant to more than a dozen pharmaceutical and medical device companies and holding stock options for Biohaven Pharmaceuticals, which is developing rimegepant.

Dr. Dodick reported serving as a consultant to Allergan, which sponsored the ubrogepant studies, as well as numerous other companies.

[email protected]

SOURCES: AHS Annual Meeting Abstracts. Alam A et al. Headache. 2018;58(Suppl 2):68. Abstract OR11; Wietecha L et al. Headache. 2018;58(Suppl 2):73. Abstract IOR02; Dodick D et al. AHS 2018 Abstract IOR01LB; Lipton R et al. AHS 2018 Abstract IOR02LB.

 

SAN FRANCISCO – After a lengthy drought in the development of major new headache medications, it was finally raining successful phase 3 clinical trials for novel drugs at the annual meeting of the American Headache Society.

Bruce Jancin/MDedge News

From the podium, as a prelude to presenting one of many positive trials, Richard B. Lipton, MD, was moved to paraphrase Charles Dickens: “ ‘It was the best of times’ ... and these are truly the best of times,” the neurologist observed.

“This morning we’ve heard about seven new molecular entities that are effective in the acute and/or preventive treatment of migraine, a couple of novel ways of delivering older drugs, and some interesting comparative effectiveness research. I have this compulsion to say over and over again – because I also work in Alzheimer’s disease – it just isn’t like this in other fields. This is truly a remarkable time in our field,” observed Dr. Lipton, professor and vice chair of the department of neurology at Albert Einstein College of Medicine in New York.

In addition to new studies of erenumab-aooe, which has been approved as Aimovig, the first-in-class calcitonin gene-related peptide (CGRP) inhibitor for the preventive treatment of migraine, the headache meeting also featured new positive phase 3 results for three other anti-CGRP monoclonal antibodies – galcanezumab, fremanezumab, and eptinezumab – as migraine-preventive therapy, with galcanezumab also demonstrating efficacy in episodic cluster headache; the oral small-molecule CGRP antagonists rimegepant and ubrogepant for acute treatment of migraine attacks; and the selective serotonin 5-HT 1F agonist lasmiditan, also for acute treatment of migraine.

Although the mechanisms of action and therapeutic purposes of the novel agents differ, they share in common what appears to be far better safety and tolerability than the current market leaders, topiramate (Topamax) for migraine prevention and the triptans for acute treatment.

Here are study highlights for the three potential new treatments for acute migraine attacks:

Rimegepant

Dr. Lipton presented the results of two virtually identical phase-3, double-blind, randomized trials in which a total of 2,162 patients with episodic migraine self-administered a 75-mg oral tablet of rimegepant or placebo to treat a single migraine attack when their headache pain reached moderate or severe intensity. The clinical trials, which lacked the customary snazzy acronyms, were simply called Study 301 and Study 302.

The two co-primary endpoints now required by the Food and Drug Administration for candidate agents for acute treatment of migraine attacks are freedom from pain and absence of the most bothersome symptom, both as assessed 2 hours post dose. The oral CGRP receptor antagonist met both endpoints, as well as key secondary endpoints.

In Study 302, for example, the pain-free rate 2 hours post dose was 19.6% in the rimegepant group, significantly higher than the 12% rate in placebo-treated controls. The rate of freedom from the most bothersome symptom, which was photophobia in the majority of patients, was 37.6% in the rimegepant group and 25.2% with placebo.

Dr. Lipton characterized the benefits seen with a single dose of rimegepant as “broad and clinically important.”

“The majority of patients achieved pain relief, durability of benefit at 24 and 48 hours, lower use of rescue medications, and a greater proportion of patients achieved normal function,” the neurologist reported.

The safety and tolerability profiles of rimegepant mirrored those of placebo, he added.

 

Ubrogepant

Dr. Lipton also presented the results of ACHIEVE II, a multicenter, double-blind, phase 3, placebo-controlled study of the oral CGRP receptor antagonist ubrogepant at 25 or 50 mg versus placebo in 1,355 patients with episodic migraine. Like rimegepant, it met both FDA-required primary endpoints. The pain freedom rate 2 hours post dose was 20.7% with ubrogepant at 25 mg, 21.8% with 50 mg, and 14.3% with placebo. The most bothersome symptom was gone at 2 hours in 34.1% of patients who received the CGRP receptor antagonist at 25 mg, 38.9% of those who got the 50-mg dose, and 27.4% of controls.

David W. Dodick, MD, explained the rationale for CGRP inhibition: CGRP and its receptors are highly expressed in pain-sensitive trigeminal sensory neurons, which innervate the dura and meningeal blood vessels. During the headache phase of migraine, the peptide is released in excess, making CGRP a key player in the pathophysiology of migraine.

Dr. Dodick presented an update focused on secondary endpoints in the phase 3, double-blind ACHIEVE I trial, whose positive co-primary outcomes have previously been reported. The analysis included 1,327 episodic migraine patients who were randomized to ubrogepant at 50 or 100 mg or placebo. Among the notable secondary outcomes was the clinically important rate of pain relief at 2 hours: 61% in both ubrogepant groups, significantly better than the 49% rate with placebo. Also, in terms of pain freedom, the 2-hour rate underestimated the true efficacy patients would experience in clinical practice: the maximum pain freedom rate occurred at 3 hours and was sustained to 8 hours post dose.

At the time study participants took their pill, only 30% indicated they were capable of functioning normally. Two hours later, this was still the case in 29.8% of placebo-treated controls, as compared with 40.6% on ubrogepant at 50 mg and 42.9% who took 100 mg of the drug. The proportion of patients who said they were satisfied or extremely satisfied with their treatment at the 2-hour mark was 24.1% in the placebo arm and 36.3% and 35.8% in the lower- and higher-dose ubrogepant arms, reported Dr. Dodick, professor of neurology at the Mayo Clinic in Scottsdale, Ariz.
 

Lasmiditan

Sheena K. Aurora, MD, presented the results of SAMURAI and SPARTAN, two randomized, double-blind, phase 3 clinical trials comparing lasmiditan versus placebo for the treatment of acute migraine in a collective 3,701 patients with longstanding episodic migraine, one-third of whom had a history of aura.

Bruce Jancin/MDedge News

Lasmiditan is a novel oral serotonin receptor agonist that penetrates the CNS and selectively targets the 5-HT 1F receptor. The drug doesn’t cause the vasoconstrictive effects that make triptans, which target 5-HT 1B/1D receptors, contraindicated in patients with cardiovascular disease.

Indeed, SPARTAN included patients with known cardiovascular disease. SAMURAI did not; however, migraine is now recognized as an independent cardiovascular risk factor, and 80% of SAMURAI participants had one additional standard cardiovascular risk factor, such as diabetes, smoking, or hypertension.

SAMURAI randomized patients to lasmiditan at 100 or 200 mg or placebo to be taken within 4 hours of migraine onset, when the pain was of at least moderate severity. SPARTAN randomized patients to lasmiditan at 50, 100, or 200 mg or placebo.

A dose-response effect was noted. At 2 hours post dose of lasmiditan at 200 mg, 32.2% of patients in SAMURAI and 38.8% in SPARTAN were pain-free, compared with 15.3% and 21.3% on placebo, respectively. At the top dose of lasmiditan, 40.7% of patients in SAMURAI were free of their most bothersome baseline symptom, as were 48.7% in SPARTAN, with placebo response rates of 29.5% and 33.5%, respectively, for this endpoint. A significant separation from placebo was noted in 1 hour for the pain freedom endpoint, and in about 30 minutes for freedom from the most bothersome symptom, reported Dr. Aurora of Eli Lilly, which sponsored the trials.

Lasmiditan at 50 and 100 mg also significantly outperformed placebo for the co-primary endpoints.

As in the phase 3 trials of the two investigational oral CGRP antagonists, a secondary endpoint in SPARTAN and SAMURAI was pain relief at 2 hours, a lower bar than pain freedom. The rates in the lasmiditan 200 mg arms were 60%-65%, compared with about 40% with placebo.

Treatment-emergent adverse event rates were 11%-15% with placebo and in the 40% range for lasmiditan. Because the drug penetrates the CNS, centrally acting side effects were an issue. Dizziness was the most common, followed by paresthesia, somnolence, then fatigue. The dizziness was dose dependent: In SPARTAN, the complaint was noted in 2.5% of placebo-treated controls, 25.4% of patients on 50 mg of lasmiditan, 36.1% with 100 mg, and 39% at 200 mg.

Chest tightness, a common side effect with triptans, did not occur.

A large multicenter, open-label safety assessment study, called GLADIATOR, is ongoing.
 

 

Triptans, what have you done for me lately?

A recurring theme at the headache meeting was the vast unmet need for better treatments for acute migraine attacks.

“You all know very well that triptans have been the most widely prescribed acute treatments for migraine in North America now for decades, but there are people with unmet treatment needs,” Dr. Lipton said. “Depending on how you define it, perhaps 34% of patients do not respond, 30%-40% have attack recurrence, and 3.5 million people have absolute or relative contraindications to triptans among the 40 million people who have migraine in the United States.”

Bruce Jancin/MDedge News

This was underscored by an analysis presented by Aftab Alam, MD, from the MAST (Migraine in America Symptoms and Treatment) study, a nationally representative cohort of 15,133 American adults with migraine and a mean monthly headache frequency of 3.3 days per month. Even though triptans are considered the gold standard acute migraine therapy, only 37% of participants in the detailed 30- to 40-minute survey had ever used a triptan, and just 15.9% of the overall study population were current users. Current triptan users averaged 7.3 headache days per month. A total of 85% of current users took oral formulations, 17% used nasal spray, and 8% utilized injectable triptans.

Among ever-users of triptans, 56.7% had discontinued them. The No.1 reason cited was lack of efficacy, named by 38% of those who stopped oral agents, 40% with the nasal spray, and 26% who discontinued injectables.

The second most common reason for triptan discontinuation was side effects, the most common of which was dizziness, followed by nausea and fatigue. Lack of insurance coverage was cited by only 6% of patients as a reason they discontinued triptans.

These MAST results suggest “there is a lot of unmet need in this area,” commented Dr. Alam, director of clinical development and medical affairs at Dr. Reddy’s Laboratories, Princeton, N.J. The MAST study was funded by Promius Pharma, a subsidiary of Dr. Reddy’s Laboratories.

Dr. Lipton reported serving as a consultant to more than a dozen pharmaceutical and medical device companies and holding stock options for Biohaven Pharmaceuticals, which is developing rimegepant.

Dr. Dodick reported serving as a consultant to Allergan, which sponsored the ubrogepant studies, as well as numerous other companies.

[email protected]

SOURCES: AHS Annual Meeting Abstracts. Alam A et al. Headache. 2018;58(Suppl 2):68. Abstract OR11; Wietecha L et al. Headache. 2018;58(Suppl 2):73. Abstract IOR02; Dodick D et al. AHS 2018 Abstract IOR01LB; Lipton R et al. AHS 2018 Abstract IOR02LB.

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Click Here to Read Content.

 

Click the link above to review hypothetical case studies that explore different monoclonal antibody (mAb) properties and the practical applications for clinical decision making.

 

For more information on mAbs, please read "The Science Behind Monoclonal Antibodies: What Neurologists Need to Know"  

 

USA-334-81078

Click Here to Read Content.

 

Click the link above to review hypothetical case studies that explore different monoclonal antibody (mAb) properties and the practical applications for clinical decision making.

 

For more information on mAbs, please read "The Science Behind Monoclonal Antibodies: What Neurologists Need to Know"  

 

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ORLANDO – The inferior outcomes associated with right-sided colon cancers might be mitigated if a higher lymph node harvest is obtained, a retrospective study suggested.

jacoblund/Thinkstock

Among patients with right-sided cancers, the rate of survival improved when 22 or more lymph nodes were harvested during operations, according to the study results presented at the American College of Surgeons Quality and Safety Conference.

“These data may provide indirect evidence for complete mesocolic excision to obtain a higher lymph node harvest to improve survival,” said investigator Arman Erkan, MD, of the Center for Colon and Rectal Surgery at Florida Hospital Orlando, in an oral abstract presentation.

This study adds new perspective on recent studies that have also demonstrated worse outcomes for right-sided versus left-sided tumors, which may be related to differences in levels of vascular ligation and nodal harvest. In addition, many studies to date have been limited in their ability to evaluate that hypothesis because of small sample size or other factors, he said in his presentation.

Accordingly, Dr. Erkan and his colleagues queried the National Cancer Database for colectomies for nonmetastatic colon adenocarcinoma occurring between 2004 and 2014, evaluating a total of 504,958 patient records, of which 273,198 were for right-sided tumors. To minimize bias, they used propensity score matching, leaving 148,540 patients in each group for the primary analysis.

Right-sided tumors were associated with inferior 5-year survival for patients with stage II and III disease (P less than .001 for right vs. left in both analyses), the investigators found.

In multivariate analysis, they found a significant interaction between right-sided tumors and a lymph node harvest of greater than 22 nodes toward increased survival, with a hazard ratio of 0.87 (95% confidence interval, 0.84-0.90). “This indicates that survival after right-sided resections can be improved if more than 22 nodes are harvested during the surgery,” Dr. Erkan said.

The difference was most pronounced in stage III of the disease, he added.

Study coauthor Lawrence Lee, MD, a colorectal surgeon at McGill University, said in a related press release that the study findings might prompt surgeons to reevaluate the types of procedures they perform in patients with right-sided tumors. “These patients may need a more extensive resection than is considered to be standard for them.”

Dr. Erkan, Dr. Lee, and other coinvestigators reported no conflicts of interest related to their research.

 

ORLANDO – The inferior outcomes associated with right-sided colon cancers might be mitigated if a higher lymph node harvest is obtained, a retrospective study suggested.

jacoblund/Thinkstock

Among patients with right-sided cancers, the rate of survival improved when 22 or more lymph nodes were harvested during operations, according to the study results presented at the American College of Surgeons Quality and Safety Conference.

“These data may provide indirect evidence for complete mesocolic excision to obtain a higher lymph node harvest to improve survival,” said investigator Arman Erkan, MD, of the Center for Colon and Rectal Surgery at Florida Hospital Orlando, in an oral abstract presentation.

This study adds new perspective on recent studies that have also demonstrated worse outcomes for right-sided versus left-sided tumors, which may be related to differences in levels of vascular ligation and nodal harvest. In addition, many studies to date have been limited in their ability to evaluate that hypothesis because of small sample size or other factors, he said in his presentation.

Accordingly, Dr. Erkan and his colleagues queried the National Cancer Database for colectomies for nonmetastatic colon adenocarcinoma occurring between 2004 and 2014, evaluating a total of 504,958 patient records, of which 273,198 were for right-sided tumors. To minimize bias, they used propensity score matching, leaving 148,540 patients in each group for the primary analysis.

Right-sided tumors were associated with inferior 5-year survival for patients with stage II and III disease (P less than .001 for right vs. left in both analyses), the investigators found.

In multivariate analysis, they found a significant interaction between right-sided tumors and a lymph node harvest of greater than 22 nodes toward increased survival, with a hazard ratio of 0.87 (95% confidence interval, 0.84-0.90). “This indicates that survival after right-sided resections can be improved if more than 22 nodes are harvested during the surgery,” Dr. Erkan said.

The difference was most pronounced in stage III of the disease, he added.

Study coauthor Lawrence Lee, MD, a colorectal surgeon at McGill University, said in a related press release that the study findings might prompt surgeons to reevaluate the types of procedures they perform in patients with right-sided tumors. “These patients may need a more extensive resection than is considered to be standard for them.”

Dr. Erkan, Dr. Lee, and other coinvestigators reported no conflicts of interest related to their research.

 

ORLANDO – The inferior outcomes associated with right-sided colon cancers might be mitigated if a higher lymph node harvest is obtained, a retrospective study suggested.

jacoblund/Thinkstock

Among patients with right-sided cancers, the rate of survival improved when 22 or more lymph nodes were harvested during operations, according to the study results presented at the American College of Surgeons Quality and Safety Conference.

“These data may provide indirect evidence for complete mesocolic excision to obtain a higher lymph node harvest to improve survival,” said investigator Arman Erkan, MD, of the Center for Colon and Rectal Surgery at Florida Hospital Orlando, in an oral abstract presentation.

This study adds new perspective on recent studies that have also demonstrated worse outcomes for right-sided versus left-sided tumors, which may be related to differences in levels of vascular ligation and nodal harvest. In addition, many studies to date have been limited in their ability to evaluate that hypothesis because of small sample size or other factors, he said in his presentation.

Accordingly, Dr. Erkan and his colleagues queried the National Cancer Database for colectomies for nonmetastatic colon adenocarcinoma occurring between 2004 and 2014, evaluating a total of 504,958 patient records, of which 273,198 were for right-sided tumors. To minimize bias, they used propensity score matching, leaving 148,540 patients in each group for the primary analysis.

Right-sided tumors were associated with inferior 5-year survival for patients with stage II and III disease (P less than .001 for right vs. left in both analyses), the investigators found.

In multivariate analysis, they found a significant interaction between right-sided tumors and a lymph node harvest of greater than 22 nodes toward increased survival, with a hazard ratio of 0.87 (95% confidence interval, 0.84-0.90). “This indicates that survival after right-sided resections can be improved if more than 22 nodes are harvested during the surgery,” Dr. Erkan said.

The difference was most pronounced in stage III of the disease, he added.

Study coauthor Lawrence Lee, MD, a colorectal surgeon at McGill University, said in a related press release that the study findings might prompt surgeons to reevaluate the types of procedures they perform in patients with right-sided tumors. “These patients may need a more extensive resection than is considered to be standard for them.”

Dr. Erkan, Dr. Lee, and other coinvestigators reported no conflicts of interest related to their research.

In March 2018, the American Gastroenterological Association (AGA) and American Association for the Study of Liver Diseases (AASLD) sponsored the Academic Skills Workshop in Charlotte, N.C. This year’s chairs Barbara Jung, MD, and Michael W. Fried, MD, FAASLD, as well as codirectors Marcia Cruz-Correa, MD, PhD, AGAF, FASGE, and Raymond Chung, MD, FAASLD, led a 2-day workshop featuring educational sessions and opportunities for mentorship and networking in academic gastroenterology and hepatology. The workshop featured sessions on how to navigate the job market, map out a career trajectory, develop fruitful mentoring relationships, apply for grant funding, and showcase research through manuscripts and oral presentations. Fellows and junior faculty from academic institutions across the United States were able to come together. Herein, two participants share their experiences at this event.

Clinical perspective from Sarah R. Lieber, MD

As a second-year gastroenterology fellow and aspiring transplant hepatologist, I found that this workshop provided an excellent framework and foundation for launching a career in academics and clinical research. It was especially effective at providing practical tips and tools for fellows and junior faculty on how to find an academic job, apply for research funding, and conduct written and oral presentations.

I was particularly moved by the personal stories and anecdotes from faculty members – many of whom are renowned leaders in the fields of GI and hepatology – who divulged the challenges and insecurities they had to overcome early in their careers. Sheila E. Crowe, MD, FRCPC, FACP, FACG, AGAF, gave an especially poignant talk on her career path from fellowship to becoming AGA president. She discussed the challenges unique to women in academic GI and hepatology, but left me feeling empowered and inspired by showcasing the many talents and success stories of her female colleagues and herself as well.

On Saturday, the AASLD held a special session that highlighted the personal stories and career trajectories of clinicians and researchers in the forefront of the field of hepatology – including AASLD president-elect Michael W. Fried, MD, FAASLD, and current AASLD President Ana Lok MD, FAASLD – among others. They emphasized the power of collaborative research that included harnessing the tools of molecular biology and Big Data to investigate the role of the microbiome and other novel subjects in liver disease. They advised us to seek out formal training when available, including master degrees or biostatistics training, to help us develop the skill sets necessary as independent researchers. They elaborated about their experiences serving on professional committees and giving oral presentations – essential to their career development – which allowed them to carve out a research niche and gain recognition as experts in their fields.

There were several powerful lessons and important themes that I take away from this workshop. The first is the importance of citizenship: Being a successful academician means not only putting in the clinical hours and being a prolific researcher but also being a good citizen. Supporting your colleagues, teaching mentees, and being a “team player” are all elements crucial to forming meaningful relationships and standing out as a valuable individual in your department. Second, perseverance is equally important; whether you are resubmitting applications for grant funding or reaching out to mentors in your area of interest, perseverance is the key to a successful career in academics. Third, remember that there is the important distinction between mentorship and sponsorship. While it is essential to have a selfless and supportive mentor who helps you cultivate your clinical and research interests, it is equally important to find a sponsor: an influential academician who can help you launch your career by acting as your advocate and opening doors to professional opportunities. Finally,you must always deliver. When mentors and sponsors give you opportunities to showcase your talents, always invest the time and effort to provide a high-quality performance. Be a good citizen who perseveres, seek out influential mentorship and sponsorship, and deliver on important professional tasks which will prime you to succeed as an academic clinical researcher in GI and hepatology.
 

 

Basic scientist perspective from Ana Maldonado-Contreras, PhD

The AGA-AASLD Workshop represented an ideal opportunity to regain perspective on my overall career plan. This year, Dr. Jung restructured the format of the program by substituting “lecture-style” sessions with fully interactive discussion panels in which trainees had the opportunity to initiate discussions about various topics of interest. The faculty leading these interactive sessions were committed to providing honest and clear answers to all of our questions. I believe this was a unique opportunity to go beyond PowerPoint presentations to actually gain insights on the dynamics of an academic department. We learned from department chairs what is considered during hiring, promoting, or allocating funds to make their team successful. Among the topics discussed, collegiality and selfless peer support were highlighted among the qualities of an appreciated department member. Panelists insisted that a balancing act between team support and one’s productivity is fundamental to thriving and maintaining focus.

Another topic with personal relevance was securing funding for my newly formed laboratory – and I was not alone! Prior to the meeting, participants were divided into small groups and assigned to a faculty mentor. Each participant was asked to share a research proposal and CV with her respective mentor. Then, each group had the opportunity to meet during the afternoon mentoring sessions. My group was composed of four participants interested in learning more about National Institutes of Health (NIH) funding strategies based on our current situations. Our assigned mentor, John Inadomi, MD – who thoroughly read our proposals and knew who we were before our encounter – provided practical advice about grant mechanisms to pursue given our current positions and provided detailed tips for successful applications. Dr. Inadomi also was greatly insightful about NIH study sessions and the entire review process. This person-to-person interaction was extremely helpful as it opened the possibility of discussing singularities of each participant’s career plans. Similarly, on the next day we had face time with David Saslowsky, PhD, program director of the National Institute of Diabetes and Digestive and Kidney Diseases at NIH. Dr. Saslowsky also reviewed our research proposals and discussed potential venues for funding within the NIDDK based on individual career trajectories.

Most of the second day was dedicated to reviewing grant opportunities and pertinent tips on how to get funded. We discussed the “most common mistakes” made by junior faculty on grant applications and ways to avoid them. All panelists agreed that the most common mistake is overambition. They advised us to critically consider the aims and activities proposed and, more importantly, seek out advice from mentors with more experience in grant writing.

Undoubtedly, networking with other peers represented an essential part of the experience at this academic workshop. As trainees, we were able to connect with not only seasoned colleagues but also with peers facing the same career challenges. Senior faculty were amazingly personable and committed to sharing experiences with the next generation of clinicians and scientists. They shared their failures, frustrations, and fears as well as their successes. Each story and the words of encouragement from this great community of scientists and clinicians helped me realize my hidden strengths and how to build from my past accomplishments to excel on my path toward becoming a fully independent researcher.
 

Dr. Lieber is a clinical epidemiology fellow, department of medicine, division of gastroenterology and hepatology, University of North Carolina (UNC), Chapel Hill; Dr. Maldonado-Contreras is an instructor in the department of microbiology and physiological systems and the Center for Microbiome Research, University of Massachusetts, Worcester.

In March 2018, the American Gastroenterological Association (AGA) and American Association for the Study of Liver Diseases (AASLD) sponsored the Academic Skills Workshop in Charlotte, N.C. This year’s chairs Barbara Jung, MD, and Michael W. Fried, MD, FAASLD, as well as codirectors Marcia Cruz-Correa, MD, PhD, AGAF, FASGE, and Raymond Chung, MD, FAASLD, led a 2-day workshop featuring educational sessions and opportunities for mentorship and networking in academic gastroenterology and hepatology. The workshop featured sessions on how to navigate the job market, map out a career trajectory, develop fruitful mentoring relationships, apply for grant funding, and showcase research through manuscripts and oral presentations. Fellows and junior faculty from academic institutions across the United States were able to come together. Herein, two participants share their experiences at this event.

Clinical perspective from Sarah R. Lieber, MD

As a second-year gastroenterology fellow and aspiring transplant hepatologist, I found that this workshop provided an excellent framework and foundation for launching a career in academics and clinical research. It was especially effective at providing practical tips and tools for fellows and junior faculty on how to find an academic job, apply for research funding, and conduct written and oral presentations.

I was particularly moved by the personal stories and anecdotes from faculty members – many of whom are renowned leaders in the fields of GI and hepatology – who divulged the challenges and insecurities they had to overcome early in their careers. Sheila E. Crowe, MD, FRCPC, FACP, FACG, AGAF, gave an especially poignant talk on her career path from fellowship to becoming AGA president. She discussed the challenges unique to women in academic GI and hepatology, but left me feeling empowered and inspired by showcasing the many talents and success stories of her female colleagues and herself as well.

On Saturday, the AASLD held a special session that highlighted the personal stories and career trajectories of clinicians and researchers in the forefront of the field of hepatology – including AASLD president-elect Michael W. Fried, MD, FAASLD, and current AASLD President Ana Lok MD, FAASLD – among others. They emphasized the power of collaborative research that included harnessing the tools of molecular biology and Big Data to investigate the role of the microbiome and other novel subjects in liver disease. They advised us to seek out formal training when available, including master degrees or biostatistics training, to help us develop the skill sets necessary as independent researchers. They elaborated about their experiences serving on professional committees and giving oral presentations – essential to their career development – which allowed them to carve out a research niche and gain recognition as experts in their fields.

There were several powerful lessons and important themes that I take away from this workshop. The first is the importance of citizenship: Being a successful academician means not only putting in the clinical hours and being a prolific researcher but also being a good citizen. Supporting your colleagues, teaching mentees, and being a “team player” are all elements crucial to forming meaningful relationships and standing out as a valuable individual in your department. Second, perseverance is equally important; whether you are resubmitting applications for grant funding or reaching out to mentors in your area of interest, perseverance is the key to a successful career in academics. Third, remember that there is the important distinction between mentorship and sponsorship. While it is essential to have a selfless and supportive mentor who helps you cultivate your clinical and research interests, it is equally important to find a sponsor: an influential academician who can help you launch your career by acting as your advocate and opening doors to professional opportunities. Finally,you must always deliver. When mentors and sponsors give you opportunities to showcase your talents, always invest the time and effort to provide a high-quality performance. Be a good citizen who perseveres, seek out influential mentorship and sponsorship, and deliver on important professional tasks which will prime you to succeed as an academic clinical researcher in GI and hepatology.
 

 

Basic scientist perspective from Ana Maldonado-Contreras, PhD

The AGA-AASLD Workshop represented an ideal opportunity to regain perspective on my overall career plan. This year, Dr. Jung restructured the format of the program by substituting “lecture-style” sessions with fully interactive discussion panels in which trainees had the opportunity to initiate discussions about various topics of interest. The faculty leading these interactive sessions were committed to providing honest and clear answers to all of our questions. I believe this was a unique opportunity to go beyond PowerPoint presentations to actually gain insights on the dynamics of an academic department. We learned from department chairs what is considered during hiring, promoting, or allocating funds to make their team successful. Among the topics discussed, collegiality and selfless peer support were highlighted among the qualities of an appreciated department member. Panelists insisted that a balancing act between team support and one’s productivity is fundamental to thriving and maintaining focus.

Another topic with personal relevance was securing funding for my newly formed laboratory – and I was not alone! Prior to the meeting, participants were divided into small groups and assigned to a faculty mentor. Each participant was asked to share a research proposal and CV with her respective mentor. Then, each group had the opportunity to meet during the afternoon mentoring sessions. My group was composed of four participants interested in learning more about National Institutes of Health (NIH) funding strategies based on our current situations. Our assigned mentor, John Inadomi, MD – who thoroughly read our proposals and knew who we were before our encounter – provided practical advice about grant mechanisms to pursue given our current positions and provided detailed tips for successful applications. Dr. Inadomi also was greatly insightful about NIH study sessions and the entire review process. This person-to-person interaction was extremely helpful as it opened the possibility of discussing singularities of each participant’s career plans. Similarly, on the next day we had face time with David Saslowsky, PhD, program director of the National Institute of Diabetes and Digestive and Kidney Diseases at NIH. Dr. Saslowsky also reviewed our research proposals and discussed potential venues for funding within the NIDDK based on individual career trajectories.

Most of the second day was dedicated to reviewing grant opportunities and pertinent tips on how to get funded. We discussed the “most common mistakes” made by junior faculty on grant applications and ways to avoid them. All panelists agreed that the most common mistake is overambition. They advised us to critically consider the aims and activities proposed and, more importantly, seek out advice from mentors with more experience in grant writing.

Undoubtedly, networking with other peers represented an essential part of the experience at this academic workshop. As trainees, we were able to connect with not only seasoned colleagues but also with peers facing the same career challenges. Senior faculty were amazingly personable and committed to sharing experiences with the next generation of clinicians and scientists. They shared their failures, frustrations, and fears as well as their successes. Each story and the words of encouragement from this great community of scientists and clinicians helped me realize my hidden strengths and how to build from my past accomplishments to excel on my path toward becoming a fully independent researcher.
 

Dr. Lieber is a clinical epidemiology fellow, department of medicine, division of gastroenterology and hepatology, University of North Carolina (UNC), Chapel Hill; Dr. Maldonado-Contreras is an instructor in the department of microbiology and physiological systems and the Center for Microbiome Research, University of Massachusetts, Worcester.

In March 2018, the American Gastroenterological Association (AGA) and American Association for the Study of Liver Diseases (AASLD) sponsored the Academic Skills Workshop in Charlotte, N.C. This year’s chairs Barbara Jung, MD, and Michael W. Fried, MD, FAASLD, as well as codirectors Marcia Cruz-Correa, MD, PhD, AGAF, FASGE, and Raymond Chung, MD, FAASLD, led a 2-day workshop featuring educational sessions and opportunities for mentorship and networking in academic gastroenterology and hepatology. The workshop featured sessions on how to navigate the job market, map out a career trajectory, develop fruitful mentoring relationships, apply for grant funding, and showcase research through manuscripts and oral presentations. Fellows and junior faculty from academic institutions across the United States were able to come together. Herein, two participants share their experiences at this event.

Clinical perspective from Sarah R. Lieber, MD

As a second-year gastroenterology fellow and aspiring transplant hepatologist, I found that this workshop provided an excellent framework and foundation for launching a career in academics and clinical research. It was especially effective at providing practical tips and tools for fellows and junior faculty on how to find an academic job, apply for research funding, and conduct written and oral presentations.

I was particularly moved by the personal stories and anecdotes from faculty members – many of whom are renowned leaders in the fields of GI and hepatology – who divulged the challenges and insecurities they had to overcome early in their careers. Sheila E. Crowe, MD, FRCPC, FACP, FACG, AGAF, gave an especially poignant talk on her career path from fellowship to becoming AGA president. She discussed the challenges unique to women in academic GI and hepatology, but left me feeling empowered and inspired by showcasing the many talents and success stories of her female colleagues and herself as well.

On Saturday, the AASLD held a special session that highlighted the personal stories and career trajectories of clinicians and researchers in the forefront of the field of hepatology – including AASLD president-elect Michael W. Fried, MD, FAASLD, and current AASLD President Ana Lok MD, FAASLD – among others. They emphasized the power of collaborative research that included harnessing the tools of molecular biology and Big Data to investigate the role of the microbiome and other novel subjects in liver disease. They advised us to seek out formal training when available, including master degrees or biostatistics training, to help us develop the skill sets necessary as independent researchers. They elaborated about their experiences serving on professional committees and giving oral presentations – essential to their career development – which allowed them to carve out a research niche and gain recognition as experts in their fields.

There were several powerful lessons and important themes that I take away from this workshop. The first is the importance of citizenship: Being a successful academician means not only putting in the clinical hours and being a prolific researcher but also being a good citizen. Supporting your colleagues, teaching mentees, and being a “team player” are all elements crucial to forming meaningful relationships and standing out as a valuable individual in your department. Second, perseverance is equally important; whether you are resubmitting applications for grant funding or reaching out to mentors in your area of interest, perseverance is the key to a successful career in academics. Third, remember that there is the important distinction between mentorship and sponsorship. While it is essential to have a selfless and supportive mentor who helps you cultivate your clinical and research interests, it is equally important to find a sponsor: an influential academician who can help you launch your career by acting as your advocate and opening doors to professional opportunities. Finally,you must always deliver. When mentors and sponsors give you opportunities to showcase your talents, always invest the time and effort to provide a high-quality performance. Be a good citizen who perseveres, seek out influential mentorship and sponsorship, and deliver on important professional tasks which will prime you to succeed as an academic clinical researcher in GI and hepatology.
 

 

Basic scientist perspective from Ana Maldonado-Contreras, PhD

The AGA-AASLD Workshop represented an ideal opportunity to regain perspective on my overall career plan. This year, Dr. Jung restructured the format of the program by substituting “lecture-style” sessions with fully interactive discussion panels in which trainees had the opportunity to initiate discussions about various topics of interest. The faculty leading these interactive sessions were committed to providing honest and clear answers to all of our questions. I believe this was a unique opportunity to go beyond PowerPoint presentations to actually gain insights on the dynamics of an academic department. We learned from department chairs what is considered during hiring, promoting, or allocating funds to make their team successful. Among the topics discussed, collegiality and selfless peer support were highlighted among the qualities of an appreciated department member. Panelists insisted that a balancing act between team support and one’s productivity is fundamental to thriving and maintaining focus.

Another topic with personal relevance was securing funding for my newly formed laboratory – and I was not alone! Prior to the meeting, participants were divided into small groups and assigned to a faculty mentor. Each participant was asked to share a research proposal and CV with her respective mentor. Then, each group had the opportunity to meet during the afternoon mentoring sessions. My group was composed of four participants interested in learning more about National Institutes of Health (NIH) funding strategies based on our current situations. Our assigned mentor, John Inadomi, MD – who thoroughly read our proposals and knew who we were before our encounter – provided practical advice about grant mechanisms to pursue given our current positions and provided detailed tips for successful applications. Dr. Inadomi also was greatly insightful about NIH study sessions and the entire review process. This person-to-person interaction was extremely helpful as it opened the possibility of discussing singularities of each participant’s career plans. Similarly, on the next day we had face time with David Saslowsky, PhD, program director of the National Institute of Diabetes and Digestive and Kidney Diseases at NIH. Dr. Saslowsky also reviewed our research proposals and discussed potential venues for funding within the NIDDK based on individual career trajectories.

Most of the second day was dedicated to reviewing grant opportunities and pertinent tips on how to get funded. We discussed the “most common mistakes” made by junior faculty on grant applications and ways to avoid them. All panelists agreed that the most common mistake is overambition. They advised us to critically consider the aims and activities proposed and, more importantly, seek out advice from mentors with more experience in grant writing.

Undoubtedly, networking with other peers represented an essential part of the experience at this academic workshop. As trainees, we were able to connect with not only seasoned colleagues but also with peers facing the same career challenges. Senior faculty were amazingly personable and committed to sharing experiences with the next generation of clinicians and scientists. They shared their failures, frustrations, and fears as well as their successes. Each story and the words of encouragement from this great community of scientists and clinicians helped me realize my hidden strengths and how to build from my past accomplishments to excel on my path toward becoming a fully independent researcher.
 

Dr. Lieber is a clinical epidemiology fellow, department of medicine, division of gastroenterology and hepatology, University of North Carolina (UNC), Chapel Hill; Dr. Maldonado-Contreras is an instructor in the department of microbiology and physiological systems and the Center for Microbiome Research, University of Massachusetts, Worcester.

Rhonda Souza, MD, AGAF, started off this session with a review of eosinophilic esophagitis (EoE). She explained the challenges of the six-food elimination diet and described an alternative step-up elimination diet. In one study of the step-up elimination diet, food triggers were identified in 88% of patients during the reintroduction of food groups. Proton pump inhibitors are recommended for patients who do not respond to or refuse diet therapy; 30%-50% of patients with EoE will respond to the drugs. She explained that PPIs might have eosinophil-reducing effects independent of gastric acid–lowering effects, and said that PPIs should be stopped for 3-4 weeks before a diagnostic endoscopy is performed if EoE is suspected. Dr. Souza also spoke about topical steroids, biologic agents, and gradual esophageal dilation.

Ronnie Fass, MD, then addressed the management of patients with documented gastroesophageal reflux disease (GERD), or heartburn without documented GERD, who are unresponsive to PPIs. He referred to the management algorithm that he and Prakash Gyawali, MD, MRCP, published this year (Gastroenterology 2018;154:302-18), and described the optimization of PPI therapy before doubling the dose, as well as the testing that should be done if the dose increase does not relieve symptoms. Dr. Fass showed that there are various possible mechanisms for refractory GERD or heartburn, including weakly acidic or alkaline reflux, functional heartburn, and reflux hypersensitivity. He reviewed the Rome IV diagnostic criteria and treatment for the latter two conditions, and discussed the role of esophageal manometry to exclude esophageal motor disorders in patients with refractory GERD and heartburn.

Colin Howden, MD, AGAF, presented data on the risks and benefits of PPIs. He reviewed the Hill criteria to prove causation and methodically reviewed whether these criteria applied to various reported risks of PPIs, from C. difficile infection and bacterial gastroenteritis to kidney disease and interference with calcium absorption. He concluded that the absolute risks are low, that most data are retrospective and prone to bias, and that causality has generally not been demonstrated. Benefit usually outweighs risk if there is a valid indication for PPI use, he said, but the lowest effective dose should be used.

Jan Tack, MD, PhD, then reviewed functional dyspepsia (FD). He described the Rome IV criteria for FD and the two main subtypes of epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), noting that some patients have both. Dr. Tack then discussed the pathophysiologic mechanisms and treatment approaches. For EPS, he recommended a trial of PPIs, then tricyclic antidepressants, and for refractory cases, behavioral therapy. For PDS, he recommended a prokinetic agent if available or acid suppression. If no response, then a 5HT1A agonist such as buspirone can be used for early satiety or mirtazapine for those with weight loss. In refractory cases, he said, a prokinetic agent such as prucalopride can be considered if there is delayed gastric emptying.

Baharak Moshiree, MD, AGAF, discussed the causes, diagnosis, and treatment of chronic nausea. Gastrointestinal causes include FD, gastroparesis, irritable bowel syndrome, celiac disease, and small intestinal bacterial overgrowth. Dr. Moshiree outlined the Rome IV criteria for chronic nausea and vomiting syndrome, cyclic vomiting syndrome, and cannabinoid hyperemesis syndrome. She also described the overlap between FD and gastroparesis and noted that nausea is a common symptom of both. Various tests can be used to rule out structural GI causes and to measure motility and gastric accommodation. In addition to treatment such as antiemetics, prokinetic agents, and neuromodulators, Dr. Moshiree examined the evidence of emerging therapies such as aprepitant, an NK1 antagonist, for gastroparesis or unexplained chronic nausea and vomiting.

Barham Abu Dayyeh, MD, MPH, addressed endoscopic management of patients after bariatric surgery. He showed that hemorrhage or marginal ulcers postsurgery can be treated with PPIs, hemoclips for bleeding ulcers, and endoscopic suturing or surgery for recalcitrant ulcers. He also discussed the management of a stenosis after Roux-en-Y gastric bypass, which now includes lumen-opposing stents, as well as the management of leaks from sleeve gastrectomy and gastric bypass and the management of biliary complications. Lastly, he reviewed the modifiable risk factors for weight regain after Roux-en-Y gastric bypass, such as gastrogastric fistula and gastrojejunal stoma dilation, and how they can be endoscopically managed.
 

 

Dr. Chang is vice-chief, Vatche and Tamar Manoukian division of digestive diseases, program director, UCLA GI fellowship program, codirector, G. Oppenheimer Center for Neurobiology of Stress and Resilience, and professor of medicine at the David Geffen School of Medicine at UCLA. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2018. She is on the advisory board for Synergy, IM HealthSciences, and Salix; an adviser for Metameconnect.com and ModifyHealth; and a speaker for Allergan and Takeda.

Rhonda Souza, MD, AGAF, started off this session with a review of eosinophilic esophagitis (EoE). She explained the challenges of the six-food elimination diet and described an alternative step-up elimination diet. In one study of the step-up elimination diet, food triggers were identified in 88% of patients during the reintroduction of food groups. Proton pump inhibitors are recommended for patients who do not respond to or refuse diet therapy; 30%-50% of patients with EoE will respond to the drugs. She explained that PPIs might have eosinophil-reducing effects independent of gastric acid–lowering effects, and said that PPIs should be stopped for 3-4 weeks before a diagnostic endoscopy is performed if EoE is suspected. Dr. Souza also spoke about topical steroids, biologic agents, and gradual esophageal dilation.

Ronnie Fass, MD, then addressed the management of patients with documented gastroesophageal reflux disease (GERD), or heartburn without documented GERD, who are unresponsive to PPIs. He referred to the management algorithm that he and Prakash Gyawali, MD, MRCP, published this year (Gastroenterology 2018;154:302-18), and described the optimization of PPI therapy before doubling the dose, as well as the testing that should be done if the dose increase does not relieve symptoms. Dr. Fass showed that there are various possible mechanisms for refractory GERD or heartburn, including weakly acidic or alkaline reflux, functional heartburn, and reflux hypersensitivity. He reviewed the Rome IV diagnostic criteria and treatment for the latter two conditions, and discussed the role of esophageal manometry to exclude esophageal motor disorders in patients with refractory GERD and heartburn.

Colin Howden, MD, AGAF, presented data on the risks and benefits of PPIs. He reviewed the Hill criteria to prove causation and methodically reviewed whether these criteria applied to various reported risks of PPIs, from C. difficile infection and bacterial gastroenteritis to kidney disease and interference with calcium absorption. He concluded that the absolute risks are low, that most data are retrospective and prone to bias, and that causality has generally not been demonstrated. Benefit usually outweighs risk if there is a valid indication for PPI use, he said, but the lowest effective dose should be used.

Jan Tack, MD, PhD, then reviewed functional dyspepsia (FD). He described the Rome IV criteria for FD and the two main subtypes of epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), noting that some patients have both. Dr. Tack then discussed the pathophysiologic mechanisms and treatment approaches. For EPS, he recommended a trial of PPIs, then tricyclic antidepressants, and for refractory cases, behavioral therapy. For PDS, he recommended a prokinetic agent if available or acid suppression. If no response, then a 5HT1A agonist such as buspirone can be used for early satiety or mirtazapine for those with weight loss. In refractory cases, he said, a prokinetic agent such as prucalopride can be considered if there is delayed gastric emptying.

Baharak Moshiree, MD, AGAF, discussed the causes, diagnosis, and treatment of chronic nausea. Gastrointestinal causes include FD, gastroparesis, irritable bowel syndrome, celiac disease, and small intestinal bacterial overgrowth. Dr. Moshiree outlined the Rome IV criteria for chronic nausea and vomiting syndrome, cyclic vomiting syndrome, and cannabinoid hyperemesis syndrome. She also described the overlap between FD and gastroparesis and noted that nausea is a common symptom of both. Various tests can be used to rule out structural GI causes and to measure motility and gastric accommodation. In addition to treatment such as antiemetics, prokinetic agents, and neuromodulators, Dr. Moshiree examined the evidence of emerging therapies such as aprepitant, an NK1 antagonist, for gastroparesis or unexplained chronic nausea and vomiting.

Barham Abu Dayyeh, MD, MPH, addressed endoscopic management of patients after bariatric surgery. He showed that hemorrhage or marginal ulcers postsurgery can be treated with PPIs, hemoclips for bleeding ulcers, and endoscopic suturing or surgery for recalcitrant ulcers. He also discussed the management of a stenosis after Roux-en-Y gastric bypass, which now includes lumen-opposing stents, as well as the management of leaks from sleeve gastrectomy and gastric bypass and the management of biliary complications. Lastly, he reviewed the modifiable risk factors for weight regain after Roux-en-Y gastric bypass, such as gastrogastric fistula and gastrojejunal stoma dilation, and how they can be endoscopically managed.
 

 

Dr. Chang is vice-chief, Vatche and Tamar Manoukian division of digestive diseases, program director, UCLA GI fellowship program, codirector, G. Oppenheimer Center for Neurobiology of Stress and Resilience, and professor of medicine at the David Geffen School of Medicine at UCLA. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2018. She is on the advisory board for Synergy, IM HealthSciences, and Salix; an adviser for Metameconnect.com and ModifyHealth; and a speaker for Allergan and Takeda.

Rhonda Souza, MD, AGAF, started off this session with a review of eosinophilic esophagitis (EoE). She explained the challenges of the six-food elimination diet and described an alternative step-up elimination diet. In one study of the step-up elimination diet, food triggers were identified in 88% of patients during the reintroduction of food groups. Proton pump inhibitors are recommended for patients who do not respond to or refuse diet therapy; 30%-50% of patients with EoE will respond to the drugs. She explained that PPIs might have eosinophil-reducing effects independent of gastric acid–lowering effects, and said that PPIs should be stopped for 3-4 weeks before a diagnostic endoscopy is performed if EoE is suspected. Dr. Souza also spoke about topical steroids, biologic agents, and gradual esophageal dilation.

Ronnie Fass, MD, then addressed the management of patients with documented gastroesophageal reflux disease (GERD), or heartburn without documented GERD, who are unresponsive to PPIs. He referred to the management algorithm that he and Prakash Gyawali, MD, MRCP, published this year (Gastroenterology 2018;154:302-18), and described the optimization of PPI therapy before doubling the dose, as well as the testing that should be done if the dose increase does not relieve symptoms. Dr. Fass showed that there are various possible mechanisms for refractory GERD or heartburn, including weakly acidic or alkaline reflux, functional heartburn, and reflux hypersensitivity. He reviewed the Rome IV diagnostic criteria and treatment for the latter two conditions, and discussed the role of esophageal manometry to exclude esophageal motor disorders in patients with refractory GERD and heartburn.

Colin Howden, MD, AGAF, presented data on the risks and benefits of PPIs. He reviewed the Hill criteria to prove causation and methodically reviewed whether these criteria applied to various reported risks of PPIs, from C. difficile infection and bacterial gastroenteritis to kidney disease and interference with calcium absorption. He concluded that the absolute risks are low, that most data are retrospective and prone to bias, and that causality has generally not been demonstrated. Benefit usually outweighs risk if there is a valid indication for PPI use, he said, but the lowest effective dose should be used.

Jan Tack, MD, PhD, then reviewed functional dyspepsia (FD). He described the Rome IV criteria for FD and the two main subtypes of epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), noting that some patients have both. Dr. Tack then discussed the pathophysiologic mechanisms and treatment approaches. For EPS, he recommended a trial of PPIs, then tricyclic antidepressants, and for refractory cases, behavioral therapy. For PDS, he recommended a prokinetic agent if available or acid suppression. If no response, then a 5HT1A agonist such as buspirone can be used for early satiety or mirtazapine for those with weight loss. In refractory cases, he said, a prokinetic agent such as prucalopride can be considered if there is delayed gastric emptying.

Baharak Moshiree, MD, AGAF, discussed the causes, diagnosis, and treatment of chronic nausea. Gastrointestinal causes include FD, gastroparesis, irritable bowel syndrome, celiac disease, and small intestinal bacterial overgrowth. Dr. Moshiree outlined the Rome IV criteria for chronic nausea and vomiting syndrome, cyclic vomiting syndrome, and cannabinoid hyperemesis syndrome. She also described the overlap between FD and gastroparesis and noted that nausea is a common symptom of both. Various tests can be used to rule out structural GI causes and to measure motility and gastric accommodation. In addition to treatment such as antiemetics, prokinetic agents, and neuromodulators, Dr. Moshiree examined the evidence of emerging therapies such as aprepitant, an NK1 antagonist, for gastroparesis or unexplained chronic nausea and vomiting.

Barham Abu Dayyeh, MD, MPH, addressed endoscopic management of patients after bariatric surgery. He showed that hemorrhage or marginal ulcers postsurgery can be treated with PPIs, hemoclips for bleeding ulcers, and endoscopic suturing or surgery for recalcitrant ulcers. He also discussed the management of a stenosis after Roux-en-Y gastric bypass, which now includes lumen-opposing stents, as well as the management of leaks from sleeve gastrectomy and gastric bypass and the management of biliary complications. Lastly, he reviewed the modifiable risk factors for weight regain after Roux-en-Y gastric bypass, such as gastrogastric fistula and gastrojejunal stoma dilation, and how they can be endoscopically managed.
 

 

Dr. Chang is vice-chief, Vatche and Tamar Manoukian division of digestive diseases, program director, UCLA GI fellowship program, codirector, G. Oppenheimer Center for Neurobiology of Stress and Resilience, and professor of medicine at the David Geffen School of Medicine at UCLA. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2018. She is on the advisory board for Synergy, IM HealthSciences, and Salix; an adviser for Metameconnect.com and ModifyHealth; and a speaker for Allergan and Takeda.

 

The large bowel session focused on functional bowel complaints, colorectal cancer risk assessment, the management of serrated polyps, and finally, the spectrum of GI side effects resulting from checkpoint inhibitor therapy.

William Chey, MD, led with a review of novel topics in irritable bowel syndrome (IBS). He emphasized the growing influence of the microbiome considerations on current thinking about IBS, in addition to the more traditional concerns regarding altered motility, visceral perception, and brain-gut interaction. He presented data demonstrating the benefit of low-FODMAP and other diets, as well as the role of antibiotic therapy in selected patients. He also reviewed early data on fecal transplants for treating IBS.

Darren Brenner, MD, reviewed current guidelines for the management of chronic constipation. He emphasized the importance of early diagnostic testing for evacuation disorders as a possible explanation for chronic constipation (for example, anorectal manometry, balloon expulsion testing). He also suggested that earlier treatment with prescription-based agents may be warranted after failure of fiber or polyethylene glycol (PEG)–based laxatives. Finally, he discussed treatment options for constipation either induced or worsened by opioid exposure.

The role of serrated polyps in colorectal carcinogenesis has been increasingly recognized. Seth Crockett, MD, reviewed the optimal means for endoscopic recognition and removal of these lesions. Colonoscopy remains the gold standard to detect serrated polyps because stool tests (blood- and DNA-based) and computed tomography colonography typically have low sensitivities to detect these lesions.

Sapna Syngal, MD, discussed the growing role of gene panel testing for patients who have colorectal cancer (CRC) or who are at elevated risk. In most settings, all newly identified CRCs are tested for microsatellite instability – a characteristic of hereditary nonpolyposis colorectal cancer (Lynch syndrome). However, with the advent of less expensive multigene, blood-based screening tests, patients can be tested for a wide variety of genetic abnormalities, some that are typically associated with CRC and others that are not. Dr. Syngal emphasized the potential effects on immediate treatment, as well as risk stratification for other diseases, associated with broad mutation testing.

Finally, Edward Loftus, MD, reviewed the GI complications associated with checkpoint inhibitor therapy, a type of immunotherapy increasingly used for a wide range of cancers. These drugs cause colitis, hepatitis, and pancreatitis, among other adverse effects. Mild cases can typically be handled (usually as in outpatient settings) with oral steroids. However, more severe toxicities may require hospitalization and intravenous, high-dose steroids. Patients with colitis who fail steroids may require infliximab or other anti–tumor necrosis factor medications, while those with hepatitis may benefit from mycophenolate.
 

Dr. Weinberg is chairman of the department of medicine at Fox Chase Cancer Center, Philadelphia. He has no conflits of interest. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2018.

 

The large bowel session focused on functional bowel complaints, colorectal cancer risk assessment, the management of serrated polyps, and finally, the spectrum of GI side effects resulting from checkpoint inhibitor therapy.

William Chey, MD, led with a review of novel topics in irritable bowel syndrome (IBS). He emphasized the growing influence of the microbiome considerations on current thinking about IBS, in addition to the more traditional concerns regarding altered motility, visceral perception, and brain-gut interaction. He presented data demonstrating the benefit of low-FODMAP and other diets, as well as the role of antibiotic therapy in selected patients. He also reviewed early data on fecal transplants for treating IBS.

Darren Brenner, MD, reviewed current guidelines for the management of chronic constipation. He emphasized the importance of early diagnostic testing for evacuation disorders as a possible explanation for chronic constipation (for example, anorectal manometry, balloon expulsion testing). He also suggested that earlier treatment with prescription-based agents may be warranted after failure of fiber or polyethylene glycol (PEG)–based laxatives. Finally, he discussed treatment options for constipation either induced or worsened by opioid exposure.

The role of serrated polyps in colorectal carcinogenesis has been increasingly recognized. Seth Crockett, MD, reviewed the optimal means for endoscopic recognition and removal of these lesions. Colonoscopy remains the gold standard to detect serrated polyps because stool tests (blood- and DNA-based) and computed tomography colonography typically have low sensitivities to detect these lesions.

Sapna Syngal, MD, discussed the growing role of gene panel testing for patients who have colorectal cancer (CRC) or who are at elevated risk. In most settings, all newly identified CRCs are tested for microsatellite instability – a characteristic of hereditary nonpolyposis colorectal cancer (Lynch syndrome). However, with the advent of less expensive multigene, blood-based screening tests, patients can be tested for a wide variety of genetic abnormalities, some that are typically associated with CRC and others that are not. Dr. Syngal emphasized the potential effects on immediate treatment, as well as risk stratification for other diseases, associated with broad mutation testing.

Finally, Edward Loftus, MD, reviewed the GI complications associated with checkpoint inhibitor therapy, a type of immunotherapy increasingly used for a wide range of cancers. These drugs cause colitis, hepatitis, and pancreatitis, among other adverse effects. Mild cases can typically be handled (usually as in outpatient settings) with oral steroids. However, more severe toxicities may require hospitalization and intravenous, high-dose steroids. Patients with colitis who fail steroids may require infliximab or other anti–tumor necrosis factor medications, while those with hepatitis may benefit from mycophenolate.
 

Dr. Weinberg is chairman of the department of medicine at Fox Chase Cancer Center, Philadelphia. He has no conflits of interest. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2018.

 

The large bowel session focused on functional bowel complaints, colorectal cancer risk assessment, the management of serrated polyps, and finally, the spectrum of GI side effects resulting from checkpoint inhibitor therapy.

William Chey, MD, led with a review of novel topics in irritable bowel syndrome (IBS). He emphasized the growing influence of the microbiome considerations on current thinking about IBS, in addition to the more traditional concerns regarding altered motility, visceral perception, and brain-gut interaction. He presented data demonstrating the benefit of low-FODMAP and other diets, as well as the role of antibiotic therapy in selected patients. He also reviewed early data on fecal transplants for treating IBS.

Darren Brenner, MD, reviewed current guidelines for the management of chronic constipation. He emphasized the importance of early diagnostic testing for evacuation disorders as a possible explanation for chronic constipation (for example, anorectal manometry, balloon expulsion testing). He also suggested that earlier treatment with prescription-based agents may be warranted after failure of fiber or polyethylene glycol (PEG)–based laxatives. Finally, he discussed treatment options for constipation either induced or worsened by opioid exposure.

The role of serrated polyps in colorectal carcinogenesis has been increasingly recognized. Seth Crockett, MD, reviewed the optimal means for endoscopic recognition and removal of these lesions. Colonoscopy remains the gold standard to detect serrated polyps because stool tests (blood- and DNA-based) and computed tomography colonography typically have low sensitivities to detect these lesions.

Sapna Syngal, MD, discussed the growing role of gene panel testing for patients who have colorectal cancer (CRC) or who are at elevated risk. In most settings, all newly identified CRCs are tested for microsatellite instability – a characteristic of hereditary nonpolyposis colorectal cancer (Lynch syndrome). However, with the advent of less expensive multigene, blood-based screening tests, patients can be tested for a wide variety of genetic abnormalities, some that are typically associated with CRC and others that are not. Dr. Syngal emphasized the potential effects on immediate treatment, as well as risk stratification for other diseases, associated with broad mutation testing.

Finally, Edward Loftus, MD, reviewed the GI complications associated with checkpoint inhibitor therapy, a type of immunotherapy increasingly used for a wide range of cancers. These drugs cause colitis, hepatitis, and pancreatitis, among other adverse effects. Mild cases can typically be handled (usually as in outpatient settings) with oral steroids. However, more severe toxicities may require hospitalization and intravenous, high-dose steroids. Patients with colitis who fail steroids may require infliximab or other anti–tumor necrosis factor medications, while those with hepatitis may benefit from mycophenolate.
 

Dr. Weinberg is chairman of the department of medicine at Fox Chase Cancer Center, Philadelphia. He has no conflits of interest. This is a summary provided by the moderator of one of the AGA Postgraduate Courses held at DDW 2018.