Mitchel L. Zoler, PhD

The mSToPS study “represents an innovative example of the potential (and challenges) inherent in a pragmatic information technology trial. The trial “represents a brave new world for clinical research: an innovative, highly commendable, contemporary pragmatic health care information technology study that tested an important question and yielded significant clinical findings,” wrote two leaders in trial design in an editorial about the study.

In addition, the mHealth Screening to Prevent Strokes (mSToPS) trial tested the utility of a wearable ECG patch to detect new-onset episodes of atrial fibrillation. Thus the study also served as one of the first examples of a trial designed to examine whether a wearable, digital device can transform health care by improving clinical outcomes, an advance that crosses the current “chasm between the technology and clinical worlds,” wrote Eric D. Peterson, MD, and Robert A. Harrington, MD. Their editorial framed mSToPS as a breakthrough in a new type of information technology–based, pragmatic clinical trial (JAMA. 2018 July 10;320[2]:137-8).

Future trials with similar designs and novel health information technology methods could tap into the enormous information contained in electronic health records, wrote Dr. Peterson, a cardiologist, professor of medicine, and executive director of the Duke Clinical Research Institute at Duke University in Durham, N.C., and Dr. Harrington, a cardiologist, professor, and chairman of medicine at Stanford (Calif.) University.

Dr. Steven R. Steinhubl, lead investigator for the mSToPS trial, agreed with this assessment. Speaking in a video interview in March 2018 during the annual scientific sessions of the American College of Cardiology, where Dr. Steinhubl first reported the mSToPS results, he characterized the trial as “completely reimagining how clinical trials are done,” by making them less expensive and more convenient for participants. In this way, mSToPS is a break from the traditional randomized clinical trial format, which creates an “artificial treatment environment and artificial patient behaviors,” said Dr. Steinhubl, a cardiologist and director of digital medicine at the Scripps Translational Science Institute in La Jolla, Calif.

Dr. Peterson has received personal fees from Livogo and has received research funding from Akili, RefleXion Medical, and Verily Life Sciences. Dr. Harrington has been a consultant to Amgen, Element Science, Gilead Sciences, MyoKardia, and WebMD; has served on the board of directors of Signal Path and Scanadu; has received personal fees from Bayer; and has received research funding from Apple, AstraZeneca, Bristol-Myers Squibb, CSL, Janssen, Novartis, Portola, Sanofi, and the Medicines Company. Dr. Steinhubl has received research funding from Janssen, DynoSense, EasyG, SpryHealth, and Striiv.

[email protected]

SOURCE: Peterson ED et al. JAMA. 2018 July 10;320[2]:138-9.

The mSToPS study “represents an innovative example of the potential (and challenges) inherent in a pragmatic information technology trial. The trial “represents a brave new world for clinical research: an innovative, highly commendable, contemporary pragmatic health care information technology study that tested an important question and yielded significant clinical findings,” wrote two leaders in trial design in an editorial about the study.

In addition, the mHealth Screening to Prevent Strokes (mSToPS) trial tested the utility of a wearable ECG patch to detect new-onset episodes of atrial fibrillation. Thus the study also served as one of the first examples of a trial designed to examine whether a wearable, digital device can transform health care by improving clinical outcomes, an advance that crosses the current “chasm between the technology and clinical worlds,” wrote Eric D. Peterson, MD, and Robert A. Harrington, MD. Their editorial framed mSToPS as a breakthrough in a new type of information technology–based, pragmatic clinical trial (JAMA. 2018 July 10;320[2]:137-8).

Future trials with similar designs and novel health information technology methods could tap into the enormous information contained in electronic health records, wrote Dr. Peterson, a cardiologist, professor of medicine, and executive director of the Duke Clinical Research Institute at Duke University in Durham, N.C., and Dr. Harrington, a cardiologist, professor, and chairman of medicine at Stanford (Calif.) University.

Dr. Steven R. Steinhubl, lead investigator for the mSToPS trial, agreed with this assessment. Speaking in a video interview in March 2018 during the annual scientific sessions of the American College of Cardiology, where Dr. Steinhubl first reported the mSToPS results, he characterized the trial as “completely reimagining how clinical trials are done,” by making them less expensive and more convenient for participants. In this way, mSToPS is a break from the traditional randomized clinical trial format, which creates an “artificial treatment environment and artificial patient behaviors,” said Dr. Steinhubl, a cardiologist and director of digital medicine at the Scripps Translational Science Institute in La Jolla, Calif.

Dr. Peterson has received personal fees from Livogo and has received research funding from Akili, RefleXion Medical, and Verily Life Sciences. Dr. Harrington has been a consultant to Amgen, Element Science, Gilead Sciences, MyoKardia, and WebMD; has served on the board of directors of Signal Path and Scanadu; has received personal fees from Bayer; and has received research funding from Apple, AstraZeneca, Bristol-Myers Squibb, CSL, Janssen, Novartis, Portola, Sanofi, and the Medicines Company. Dr. Steinhubl has received research funding from Janssen, DynoSense, EasyG, SpryHealth, and Striiv.

[email protected]

SOURCE: Peterson ED et al. JAMA. 2018 July 10;320[2]:138-9.

The mSToPS study “represents an innovative example of the potential (and challenges) inherent in a pragmatic information technology trial. The trial “represents a brave new world for clinical research: an innovative, highly commendable, contemporary pragmatic health care information technology study that tested an important question and yielded significant clinical findings,” wrote two leaders in trial design in an editorial about the study.

In addition, the mHealth Screening to Prevent Strokes (mSToPS) trial tested the utility of a wearable ECG patch to detect new-onset episodes of atrial fibrillation. Thus the study also served as one of the first examples of a trial designed to examine whether a wearable, digital device can transform health care by improving clinical outcomes, an advance that crosses the current “chasm between the technology and clinical worlds,” wrote Eric D. Peterson, MD, and Robert A. Harrington, MD. Their editorial framed mSToPS as a breakthrough in a new type of information technology–based, pragmatic clinical trial (JAMA. 2018 July 10;320[2]:137-8).

Future trials with similar designs and novel health information technology methods could tap into the enormous information contained in electronic health records, wrote Dr. Peterson, a cardiologist, professor of medicine, and executive director of the Duke Clinical Research Institute at Duke University in Durham, N.C., and Dr. Harrington, a cardiologist, professor, and chairman of medicine at Stanford (Calif.) University.

Dr. Steven R. Steinhubl, lead investigator for the mSToPS trial, agreed with this assessment. Speaking in a video interview in March 2018 during the annual scientific sessions of the American College of Cardiology, where Dr. Steinhubl first reported the mSToPS results, he characterized the trial as “completely reimagining how clinical trials are done,” by making them less expensive and more convenient for participants. In this way, mSToPS is a break from the traditional randomized clinical trial format, which creates an “artificial treatment environment and artificial patient behaviors,” said Dr. Steinhubl, a cardiologist and director of digital medicine at the Scripps Translational Science Institute in La Jolla, Calif.

Dr. Peterson has received personal fees from Livogo and has received research funding from Akili, RefleXion Medical, and Verily Life Sciences. Dr. Harrington has been a consultant to Amgen, Element Science, Gilead Sciences, MyoKardia, and WebMD; has served on the board of directors of Signal Path and Scanadu; has received personal fees from Bayer; and has received research funding from Apple, AstraZeneca, Bristol-Myers Squibb, CSL, Janssen, Novartis, Portola, Sanofi, and the Medicines Company. Dr. Steinhubl has received research funding from Janssen, DynoSense, EasyG, SpryHealth, and Striiv.

[email protected]

SOURCE: Peterson ED et al. JAMA. 2018 July 10;320[2]:138-9.

WASHINGTON – A majority of U.S. patients with presumed exocrine pancreatic insufficiency are likely going undiagnosed and untreated, and even those who get enzyme replacement therapy often receive too little, according to a recent analysis of insurance claims data from more than 48 million Americans.

Amid concerns that some people with nonspecific symptoms are overdiagnosed with exocrine pancreatic insufficiency (EPI) and hence getting unneeded treatment with pancreatic enzyme replacement therapy (PERT), it seems like substantial numbers of patients with legitimate pancreatic morbidity are often missed and are going untreated, Chris E. Forsmark, MD, said at the annual Digestive Disease Week^®. This includes patients with chronic pancreatitis, pancreatic cancer, and patients who underwent pancreatic resection surgery.

Mitchel L. Zoler/MDedge News

[email protected]

WASHINGTON – A majority of U.S. patients with presumed exocrine pancreatic insufficiency are likely going undiagnosed and untreated, and even those who get enzyme replacement therapy often receive too little, according to a recent analysis of insurance claims data from more than 48 million Americans.

Amid concerns that some people with nonspecific symptoms are overdiagnosed with exocrine pancreatic insufficiency (EPI) and hence getting unneeded treatment with pancreatic enzyme replacement therapy (PERT), it seems like substantial numbers of patients with legitimate pancreatic morbidity are often missed and are going untreated, Chris E. Forsmark, MD, said at the annual Digestive Disease Week^®. This includes patients with chronic pancreatitis, pancreatic cancer, and patients who underwent pancreatic resection surgery.

Mitchel L. Zoler/MDedge News

[email protected]

WASHINGTON – A majority of U.S. patients with presumed exocrine pancreatic insufficiency are likely going undiagnosed and untreated, and even those who get enzyme replacement therapy often receive too little, according to a recent analysis of insurance claims data from more than 48 million Americans.

Amid concerns that some people with nonspecific symptoms are overdiagnosed with exocrine pancreatic insufficiency (EPI) and hence getting unneeded treatment with pancreatic enzyme replacement therapy (PERT), it seems like substantial numbers of patients with legitimate pancreatic morbidity are often missed and are going untreated, Chris E. Forsmark, MD, said at the annual Digestive Disease Week^®. This includes patients with chronic pancreatitis, pancreatic cancer, and patients who underwent pancreatic resection surgery.

Mitchel L. Zoler/MDedge News

[email protected]

AMSTERDAM – The first recommendations from a rheumatology society for managing patients with Sjögren’s syndrome are nearing finalization by a EULAR task force, and they divide the treatment targets into sicca syndrome and systemic manifestations of the disease.

“In Sjögren’s, we always have two subtypes of patients: those who have sicca syndrome only, and those with sicca syndrome plus systemic disease,” explained Soledad Retamozo, MD, who presented the current version of the recommendations at the European Congress of Rheumatology. “We wanted to highlight that there are two types of patients,” said Dr. Retamozo, a rheumatologist at the University of Córdoba (Argentina). “It’s hard to treat patients with sicca syndrome plus fatigue and pain because there is no high-level evidence on how to do this; all we have is expert opinion,” Dr. Retamozo said in an interview.

Mitchel L. Zoler/MDedge News

In fact, roughly half of the recommendations have no supporting evidence base, as presented by Dr. Retamozo. That starts with all three general recommendations she presented:

• Patients with Sjögren’s should be managed at a center of expertise using a multidisciplinary approach, which she said should include ophthalmologists and dentists to help address the mouth and ocular manifestations of sicca syndrome.

• Patients with sicca syndrome should receive symptomatic relief with topical treatments.

• Systemic treatments – glucocorticoids, immunosuppressants, and biologicals – can be considered for patients with active systemic disease.

The statement’s specific recommendations start with managing oral dryness, an intervention that should begin by measuring salivary gland (SG) dysfunction. The document next recommends nonpharmacologic interventions for mild SG dysfunction, pharmacological stimulation for moderate SG dysfunction, and a saliva substitute for severe SG dysfunction. All three recommendations are evidence based, relying on results from either randomized trials or controlled studies.

The second target for topical treatments is ocular dryness, which starts with artificial tears, or ocular gels or ointments, recommendations based on randomized trials. Refractory or severe ocular dryness should receive eye drops that contain a nonsteroidal anti-inflammatory drug or a glucocorticoid, based on controlled study results, or autologous serum eye drops, a strategy tested in a randomized trial.

The recommendations then shift to dealing with systemic manifestations, starting with fatigue and pain, offering the expert recommendation to evaluate the contribution of comorbid diseases and assess their severity with tools such as the Eular Sjögren’s Syndrome Patient-Reported Index (ESSPRI) (Ann Rheum Dis. 2011 June;70[6]:968-72), the Profile of Fatigue, and the Brief Pain Inventory.

Using evidence from randomized trials, the recommendations tell clinicians to consider treatment with analgesics or pain-modifying agents for musculoskeletal pain by weighing the potential benefits and adverse effects from this treatment.

For other forms of systemic disease, the recommendations offer the expert opinion to tailor treatment to the organ-specific severity using the ESSPRI definitions. If using glucocorticoids to treat systemic disease, they should be given at the minimum effective dose and for the shortest period of time needed to control active systemic disease, a recommendation based on retrospective or descriptive studies. Expert opinion called for using immunosuppressive treatments as glucocorticoid-sparing options for systemic disease, and this recommendation added that no particular immunosuppressive agent stands out as best compared with all available agents. In more than 95% of reported cases of systemic disease treatment in Sjögren’s patients, clinicians used the immunosuppressive drugs in association with glucocorticoids, Dr. Retamozo noted.

Finally, for systemic disease the recommendations cited evidence from controlled studies that B-cell targeted therapies, such as rituximab (Rituxan) and belimumab (Benlysta), may be considered in patients with severe, refractory systemic disease. An additional expert opinion was that the systemic, organ-specific approach should sequence treatments by using glucocorticoids first, followed by immunosuppressants, and finally biological drugs.

The recommendations finish with an entry that treatment of B-cell lymphoma be individualized based on the specific histopathologic subtype involved and the level of disease extension, an approach based on results from retrospective or descriptive studies.

The recommendations must still undergo final EULAR review and endorsement, with publication on track to occur before the end of 2018, Dr. Retamozo said.

She had no disclosures.

[email protected]

SOURCE: Retamozo S al. Ann Rheum Dis. 2018;77(Suppl 2):42. Abstract SP0159.

AMSTERDAM – The first recommendations from a rheumatology society for managing patients with Sjögren’s syndrome are nearing finalization by a EULAR task force, and they divide the treatment targets into sicca syndrome and systemic manifestations of the disease.

“In Sjögren’s, we always have two subtypes of patients: those who have sicca syndrome only, and those with sicca syndrome plus systemic disease,” explained Soledad Retamozo, MD, who presented the current version of the recommendations at the European Congress of Rheumatology. “We wanted to highlight that there are two types of patients,” said Dr. Retamozo, a rheumatologist at the University of Córdoba (Argentina). “It’s hard to treat patients with sicca syndrome plus fatigue and pain because there is no high-level evidence on how to do this; all we have is expert opinion,” Dr. Retamozo said in an interview.

Mitchel L. Zoler/MDedge News

In fact, roughly half of the recommendations have no supporting evidence base, as presented by Dr. Retamozo. That starts with all three general recommendations she presented:

• Patients with Sjögren’s should be managed at a center of expertise using a multidisciplinary approach, which she said should include ophthalmologists and dentists to help address the mouth and ocular manifestations of sicca syndrome.

• Patients with sicca syndrome should receive symptomatic relief with topical treatments.

• Systemic treatments – glucocorticoids, immunosuppressants, and biologicals – can be considered for patients with active systemic disease.

The statement’s specific recommendations start with managing oral dryness, an intervention that should begin by measuring salivary gland (SG) dysfunction. The document next recommends nonpharmacologic interventions for mild SG dysfunction, pharmacological stimulation for moderate SG dysfunction, and a saliva substitute for severe SG dysfunction. All three recommendations are evidence based, relying on results from either randomized trials or controlled studies.

The second target for topical treatments is ocular dryness, which starts with artificial tears, or ocular gels or ointments, recommendations based on randomized trials. Refractory or severe ocular dryness should receive eye drops that contain a nonsteroidal anti-inflammatory drug or a glucocorticoid, based on controlled study results, or autologous serum eye drops, a strategy tested in a randomized trial.

The recommendations then shift to dealing with systemic manifestations, starting with fatigue and pain, offering the expert recommendation to evaluate the contribution of comorbid diseases and assess their severity with tools such as the Eular Sjögren’s Syndrome Patient-Reported Index (ESSPRI) (Ann Rheum Dis. 2011 June;70[6]:968-72), the Profile of Fatigue, and the Brief Pain Inventory.

Using evidence from randomized trials, the recommendations tell clinicians to consider treatment with analgesics or pain-modifying agents for musculoskeletal pain by weighing the potential benefits and adverse effects from this treatment.

For other forms of systemic disease, the recommendations offer the expert opinion to tailor treatment to the organ-specific severity using the ESSPRI definitions. If using glucocorticoids to treat systemic disease, they should be given at the minimum effective dose and for the shortest period of time needed to control active systemic disease, a recommendation based on retrospective or descriptive studies. Expert opinion called for using immunosuppressive treatments as glucocorticoid-sparing options for systemic disease, and this recommendation added that no particular immunosuppressive agent stands out as best compared with all available agents. In more than 95% of reported cases of systemic disease treatment in Sjögren’s patients, clinicians used the immunosuppressive drugs in association with glucocorticoids, Dr. Retamozo noted.

Finally, for systemic disease the recommendations cited evidence from controlled studies that B-cell targeted therapies, such as rituximab (Rituxan) and belimumab (Benlysta), may be considered in patients with severe, refractory systemic disease. An additional expert opinion was that the systemic, organ-specific approach should sequence treatments by using glucocorticoids first, followed by immunosuppressants, and finally biological drugs.

The recommendations finish with an entry that treatment of B-cell lymphoma be individualized based on the specific histopathologic subtype involved and the level of disease extension, an approach based on results from retrospective or descriptive studies.

The recommendations must still undergo final EULAR review and endorsement, with publication on track to occur before the end of 2018, Dr. Retamozo said.

She had no disclosures.

[email protected]

SOURCE: Retamozo S al. Ann Rheum Dis. 2018;77(Suppl 2):42. Abstract SP0159.

AMSTERDAM – The first recommendations from a rheumatology society for managing patients with Sjögren’s syndrome are nearing finalization by a EULAR task force, and they divide the treatment targets into sicca syndrome and systemic manifestations of the disease.

“In Sjögren’s, we always have two subtypes of patients: those who have sicca syndrome only, and those with sicca syndrome plus systemic disease,” explained Soledad Retamozo, MD, who presented the current version of the recommendations at the European Congress of Rheumatology. “We wanted to highlight that there are two types of patients,” said Dr. Retamozo, a rheumatologist at the University of Córdoba (Argentina). “It’s hard to treat patients with sicca syndrome plus fatigue and pain because there is no high-level evidence on how to do this; all we have is expert opinion,” Dr. Retamozo said in an interview.

Mitchel L. Zoler/MDedge News

In fact, roughly half of the recommendations have no supporting evidence base, as presented by Dr. Retamozo. That starts with all three general recommendations she presented:

• Patients with Sjögren’s should be managed at a center of expertise using a multidisciplinary approach, which she said should include ophthalmologists and dentists to help address the mouth and ocular manifestations of sicca syndrome.

• Patients with sicca syndrome should receive symptomatic relief with topical treatments.

• Systemic treatments – glucocorticoids, immunosuppressants, and biologicals – can be considered for patients with active systemic disease.

The statement’s specific recommendations start with managing oral dryness, an intervention that should begin by measuring salivary gland (SG) dysfunction. The document next recommends nonpharmacologic interventions for mild SG dysfunction, pharmacological stimulation for moderate SG dysfunction, and a saliva substitute for severe SG dysfunction. All three recommendations are evidence based, relying on results from either randomized trials or controlled studies.

The second target for topical treatments is ocular dryness, which starts with artificial tears, or ocular gels or ointments, recommendations based on randomized trials. Refractory or severe ocular dryness should receive eye drops that contain a nonsteroidal anti-inflammatory drug or a glucocorticoid, based on controlled study results, or autologous serum eye drops, a strategy tested in a randomized trial.

The recommendations then shift to dealing with systemic manifestations, starting with fatigue and pain, offering the expert recommendation to evaluate the contribution of comorbid diseases and assess their severity with tools such as the Eular Sjögren’s Syndrome Patient-Reported Index (ESSPRI) (Ann Rheum Dis. 2011 June;70[6]:968-72), the Profile of Fatigue, and the Brief Pain Inventory.

Using evidence from randomized trials, the recommendations tell clinicians to consider treatment with analgesics or pain-modifying agents for musculoskeletal pain by weighing the potential benefits and adverse effects from this treatment.

For other forms of systemic disease, the recommendations offer the expert opinion to tailor treatment to the organ-specific severity using the ESSPRI definitions. If using glucocorticoids to treat systemic disease, they should be given at the minimum effective dose and for the shortest period of time needed to control active systemic disease, a recommendation based on retrospective or descriptive studies. Expert opinion called for using immunosuppressive treatments as glucocorticoid-sparing options for systemic disease, and this recommendation added that no particular immunosuppressive agent stands out as best compared with all available agents. In more than 95% of reported cases of systemic disease treatment in Sjögren’s patients, clinicians used the immunosuppressive drugs in association with glucocorticoids, Dr. Retamozo noted.

Finally, for systemic disease the recommendations cited evidence from controlled studies that B-cell targeted therapies, such as rituximab (Rituxan) and belimumab (Benlysta), may be considered in patients with severe, refractory systemic disease. An additional expert opinion was that the systemic, organ-specific approach should sequence treatments by using glucocorticoids first, followed by immunosuppressants, and finally biological drugs.

The recommendations finish with an entry that treatment of B-cell lymphoma be individualized based on the specific histopathologic subtype involved and the level of disease extension, an approach based on results from retrospective or descriptive studies.

The recommendations must still undergo final EULAR review and endorsement, with publication on track to occur before the end of 2018, Dr. Retamozo said.

She had no disclosures.

[email protected]

SOURCE: Retamozo S al. Ann Rheum Dis. 2018;77(Suppl 2):42. Abstract SP0159.

WASHINGTON – Patients with cirrhosis who received secondary prophylaxis for spontaneous bacterial peritonitis had better outcomes than patients who received primary prophylaxis in a review of more than 300 patients at 14 North American centers.

The mortality rate during follow-up of cirrhotic patients hospitalized while on primary prophylaxis against spontaneous bacterial peritonitis (SBP) was 19%, compared with a 9% death rate among cirrhotic patients hospitalized while on secondary prophylaxis, Jasmohan S. Bajaj, MD, said at the annual Digestive Disease Week^®.

Although the findings raised questions about the value of primary prophylaxis with an antibiotic in cirrhotic patients for preventing a first episode of SBP, secondary prophylaxis remains an important precaution.

“There is clear benefit from secondary prophylaxis; please use it. The data supporting it are robust,” said Dr. Bajaj, a hepatologist at Virginia Commonwealth University, Richmond. In contrast, the evidence supporting benefits from primary prophylaxis is weaker, he said. The findings were also counterintuitive, because patients who experience repeat episodes of SBP might be expected to fare worse than those hit by SBP just once.

Dr. Bajaj also acknowledged the substantial confounding that distinguishes patients with cirrhosis receiving primary or secondary prophylaxis, and the difficulty of fully adjusting for all this confounding by statistical analyses. “There is selective bias for secondary prevention, and there is no way to correct for this,” he explained. Patients who need secondary prophylaxis have “weathered the storm” of a first episode of SBP, which might have exerted selection pressure, and might have triggered important immunologic changes, Dr. Bajaj suggested.

The findings also raised concerns about the appropriateness of existing antibiotic prophylaxis for SBP. The patients included in the study all received similar regimens regardless of whether they were on primary or secondary prophylaxis. Three-quarters of primary prophylaxis patients received a fluoroquinolone, as did 81% on secondary prophylaxis. All other patients received trimethoprim-sulfamethoxazole. These regimens are aimed at preventing gram-negative infections; however, an increasing number of SBP episodes are caused by either gram-positive pathogens or strains of gram-negative bacteria or fungi resistant to standard antibiotics.

Clinicians “absolutely” need to rethink their approach to both primary and secondary prophylaxis, Dr. Bajaj said. “As fast as treatment evolves, bacteria evolve 20 times faster. We need to find ways to prevent infections without antibiotic prophylaxis, whatever that might be.”

The study used data collected prospectively from patients with cirrhosis at any of 12 U.S. and 2 Canadian centers that belonged to the North American Consortium for the Study of End-Stage Liver Disease. Among 2,731 cirrhotic patients admitted nonelectively, 492 (18%) were on antibiotic prophylaxis at the time of their admission, 305 for primary prophylaxis and 187 for secondary prophylaxis. Dr. Bajaj and his associates used both the baseline model for end-stage liver disease score and serum albumin level of each patient to focus on a group of 154 primary prophylaxis and 154 secondary prophylaxis patients who were similar by these two criteria. Despite this matching, the two subgroups showed statistically significant differences at the time of their index hospitalization for several important clinical measures.

The secondary prophylaxis patients were significantly more likely to have been hospitalized within the previous 6 months, significantly more likely to be on treatment for hepatic encephalopathy at the time of their index admission, and significantly less likely to have systemic inflammatory response syndrome on admission.

Also, at the time of admission, secondary prophylaxis patients were significantly more likely to have an infection of any type at a rate of 40%, compared with 24% among those on primary prophylaxis, as well as a significantly higher rate of SBP at 16%, compared with a 9% rate among the primary prophylaxis patients. During hospitalization, nosocomial SBP occurred significantly more often among the secondary prophylaxis patients at a rate of 6%, compared with a 0.5% rate among those on primary prophylaxis.

Despite these between-group differences, the average duration of hospitalization, and the average incidence of acute-on-chronic liver failure during follow-up out to 30 days post discharge was similar in the two subgroups. And the patients on secondary prophylaxis showed better outcomes by two important parameters: mortality during hospitalization and 30 days post discharge; and the incidence of ICU admission during hospitalization, which was significantly greater for primary prophylaxis patients at 31%, compared with 21% among the secondary prophylaxis patients, Dr. Bajaj reported.

Dr. Bajaj has been a consultant for Norgine and Salix Pharmaceuticals and has received research support from Grifols and Salix Pharmaceuticals.

[email protected]

WASHINGTON – Patients with cirrhosis who received secondary prophylaxis for spontaneous bacterial peritonitis had better outcomes than patients who received primary prophylaxis in a review of more than 300 patients at 14 North American centers.

The mortality rate during follow-up of cirrhotic patients hospitalized while on primary prophylaxis against spontaneous bacterial peritonitis (SBP) was 19%, compared with a 9% death rate among cirrhotic patients hospitalized while on secondary prophylaxis, Jasmohan S. Bajaj, MD, said at the annual Digestive Disease Week^®.

Although the findings raised questions about the value of primary prophylaxis with an antibiotic in cirrhotic patients for preventing a first episode of SBP, secondary prophylaxis remains an important precaution.

“There is clear benefit from secondary prophylaxis; please use it. The data supporting it are robust,” said Dr. Bajaj, a hepatologist at Virginia Commonwealth University, Richmond. In contrast, the evidence supporting benefits from primary prophylaxis is weaker, he said. The findings were also counterintuitive, because patients who experience repeat episodes of SBP might be expected to fare worse than those hit by SBP just once.

Dr. Bajaj also acknowledged the substantial confounding that distinguishes patients with cirrhosis receiving primary or secondary prophylaxis, and the difficulty of fully adjusting for all this confounding by statistical analyses. “There is selective bias for secondary prevention, and there is no way to correct for this,” he explained. Patients who need secondary prophylaxis have “weathered the storm” of a first episode of SBP, which might have exerted selection pressure, and might have triggered important immunologic changes, Dr. Bajaj suggested.

The findings also raised concerns about the appropriateness of existing antibiotic prophylaxis for SBP. The patients included in the study all received similar regimens regardless of whether they were on primary or secondary prophylaxis. Three-quarters of primary prophylaxis patients received a fluoroquinolone, as did 81% on secondary prophylaxis. All other patients received trimethoprim-sulfamethoxazole. These regimens are aimed at preventing gram-negative infections; however, an increasing number of SBP episodes are caused by either gram-positive pathogens or strains of gram-negative bacteria or fungi resistant to standard antibiotics.

Clinicians “absolutely” need to rethink their approach to both primary and secondary prophylaxis, Dr. Bajaj said. “As fast as treatment evolves, bacteria evolve 20 times faster. We need to find ways to prevent infections without antibiotic prophylaxis, whatever that might be.”

The study used data collected prospectively from patients with cirrhosis at any of 12 U.S. and 2 Canadian centers that belonged to the North American Consortium for the Study of End-Stage Liver Disease. Among 2,731 cirrhotic patients admitted nonelectively, 492 (18%) were on antibiotic prophylaxis at the time of their admission, 305 for primary prophylaxis and 187 for secondary prophylaxis. Dr. Bajaj and his associates used both the baseline model for end-stage liver disease score and serum albumin level of each patient to focus on a group of 154 primary prophylaxis and 154 secondary prophylaxis patients who were similar by these two criteria. Despite this matching, the two subgroups showed statistically significant differences at the time of their index hospitalization for several important clinical measures.

The secondary prophylaxis patients were significantly more likely to have been hospitalized within the previous 6 months, significantly more likely to be on treatment for hepatic encephalopathy at the time of their index admission, and significantly less likely to have systemic inflammatory response syndrome on admission.

Also, at the time of admission, secondary prophylaxis patients were significantly more likely to have an infection of any type at a rate of 40%, compared with 24% among those on primary prophylaxis, as well as a significantly higher rate of SBP at 16%, compared with a 9% rate among the primary prophylaxis patients. During hospitalization, nosocomial SBP occurred significantly more often among the secondary prophylaxis patients at a rate of 6%, compared with a 0.5% rate among those on primary prophylaxis.

Despite these between-group differences, the average duration of hospitalization, and the average incidence of acute-on-chronic liver failure during follow-up out to 30 days post discharge was similar in the two subgroups. And the patients on secondary prophylaxis showed better outcomes by two important parameters: mortality during hospitalization and 30 days post discharge; and the incidence of ICU admission during hospitalization, which was significantly greater for primary prophylaxis patients at 31%, compared with 21% among the secondary prophylaxis patients, Dr. Bajaj reported.

Dr. Bajaj has been a consultant for Norgine and Salix Pharmaceuticals and has received research support from Grifols and Salix Pharmaceuticals.

[email protected]

WASHINGTON – Patients with cirrhosis who received secondary prophylaxis for spontaneous bacterial peritonitis had better outcomes than patients who received primary prophylaxis in a review of more than 300 patients at 14 North American centers.

The mortality rate during follow-up of cirrhotic patients hospitalized while on primary prophylaxis against spontaneous bacterial peritonitis (SBP) was 19%, compared with a 9% death rate among cirrhotic patients hospitalized while on secondary prophylaxis, Jasmohan S. Bajaj, MD, said at the annual Digestive Disease Week^®.

Although the findings raised questions about the value of primary prophylaxis with an antibiotic in cirrhotic patients for preventing a first episode of SBP, secondary prophylaxis remains an important precaution.

“There is clear benefit from secondary prophylaxis; please use it. The data supporting it are robust,” said Dr. Bajaj, a hepatologist at Virginia Commonwealth University, Richmond. In contrast, the evidence supporting benefits from primary prophylaxis is weaker, he said. The findings were also counterintuitive, because patients who experience repeat episodes of SBP might be expected to fare worse than those hit by SBP just once.

Dr. Bajaj also acknowledged the substantial confounding that distinguishes patients with cirrhosis receiving primary or secondary prophylaxis, and the difficulty of fully adjusting for all this confounding by statistical analyses. “There is selective bias for secondary prevention, and there is no way to correct for this,” he explained. Patients who need secondary prophylaxis have “weathered the storm” of a first episode of SBP, which might have exerted selection pressure, and might have triggered important immunologic changes, Dr. Bajaj suggested.

The findings also raised concerns about the appropriateness of existing antibiotic prophylaxis for SBP. The patients included in the study all received similar regimens regardless of whether they were on primary or secondary prophylaxis. Three-quarters of primary prophylaxis patients received a fluoroquinolone, as did 81% on secondary prophylaxis. All other patients received trimethoprim-sulfamethoxazole. These regimens are aimed at preventing gram-negative infections; however, an increasing number of SBP episodes are caused by either gram-positive pathogens or strains of gram-negative bacteria or fungi resistant to standard antibiotics.

Clinicians “absolutely” need to rethink their approach to both primary and secondary prophylaxis, Dr. Bajaj said. “As fast as treatment evolves, bacteria evolve 20 times faster. We need to find ways to prevent infections without antibiotic prophylaxis, whatever that might be.”

The study used data collected prospectively from patients with cirrhosis at any of 12 U.S. and 2 Canadian centers that belonged to the North American Consortium for the Study of End-Stage Liver Disease. Among 2,731 cirrhotic patients admitted nonelectively, 492 (18%) were on antibiotic prophylaxis at the time of their admission, 305 for primary prophylaxis and 187 for secondary prophylaxis. Dr. Bajaj and his associates used both the baseline model for end-stage liver disease score and serum albumin level of each patient to focus on a group of 154 primary prophylaxis and 154 secondary prophylaxis patients who were similar by these two criteria. Despite this matching, the two subgroups showed statistically significant differences at the time of their index hospitalization for several important clinical measures.

The secondary prophylaxis patients were significantly more likely to have been hospitalized within the previous 6 months, significantly more likely to be on treatment for hepatic encephalopathy at the time of their index admission, and significantly less likely to have systemic inflammatory response syndrome on admission.

Also, at the time of admission, secondary prophylaxis patients were significantly more likely to have an infection of any type at a rate of 40%, compared with 24% among those on primary prophylaxis, as well as a significantly higher rate of SBP at 16%, compared with a 9% rate among the primary prophylaxis patients. During hospitalization, nosocomial SBP occurred significantly more often among the secondary prophylaxis patients at a rate of 6%, compared with a 0.5% rate among those on primary prophylaxis.

Despite these between-group differences, the average duration of hospitalization, and the average incidence of acute-on-chronic liver failure during follow-up out to 30 days post discharge was similar in the two subgroups. And the patients on secondary prophylaxis showed better outcomes by two important parameters: mortality during hospitalization and 30 days post discharge; and the incidence of ICU admission during hospitalization, which was significantly greater for primary prophylaxis patients at 31%, compared with 21% among the secondary prophylaxis patients, Dr. Bajaj reported.

Dr. Bajaj has been a consultant for Norgine and Salix Pharmaceuticals and has received research support from Grifols and Salix Pharmaceuticals.

[email protected]

AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.

The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.

AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.

The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.

AMSTERDAM – Patients with rheumatoid arthritis who had a high serum level of biologic immunomodulatory drugs had a statistically significant 51% higher rate of infection during their first year on the drug, compared with RA patients who maintained usual or low serum levels of the same drugs, according to an analysis of 703 U.K. patients in a national database.

The results suggest that, once patients with rheumatoid arthritis go into remission on a higher dosage of biologic agents that produce a high serum level “dose tapering may lower their risk of infection,” Meghna Jani, MD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/MDedge News

Mitchel L. Zoler/MDedge News

[email protected]

SOURCE: Jani M et al. EULAR 2018 Congress, Abstract OP0229.

AMSTERDAM – Starting patients with newly diagnosed, peripheral spondyloarthritis (SpA) on treatment with a tumor necrosis factor (TNF) inhibitor within 12 weeks of symptom onset produced an “amazing,” long-term, complete remission that resembled cure in more than half of the 40 treated patients, a finding that now needs replication in a larger, multicenter study, Philippe Carron, MD, said at the European Congress of Rheumatology.

Ongoing research on patients in the original study cohort also showed that methotrexate is largely ineffective to help wean patients in remission on a tumor necrosis factor inhibitor off the biologic drug, said Dr. Carron, a rheumatologist at the University of Ghent (Belgium). In his group’s most recent experience with 22 patients in remission on a regimen of golimumab and methotrexate, 5 remained in remission (23%) when golimumab treatment stopped, whereas the other 17 patients had to restart golimumab (Simponi) while continuing on methotrexate after relapsing on methotrexate monotherapy, Dr. Carron reported.

Mitchel L. Zoler/MDedge News

Methotrexate has “overall weak efficacy for maintaining biological-free remission” in patients with peripheral SpA, he concluded.

But Dr. Carron remained very positive about the main finding of the CRESPA (Clinical Remission in Patients with Early Peripheral Spondyloarthritis) study, which has now shown a durable complete remission – free from arthritis, enthesitis, and dactylitis – in 21 of 40 (53%) patients who began golimumab treatment within 12 weeks of their symptom onset and then remained in remission when the golimumab was eventually stopped. These patients have now remained in complete remission for 2.4-5.8 years of follow-up, Dr. Carron said. He attributed this very durable remission while off any treatment to the rapid start of TNF-inhibitor therapy within weeks of their symptom onset.

“This is fantastic; these patients are cured. Early treatment is the most important reason why the result is so good,” but it also poses the biggest challenge for using this approach in routine practice, Dr. Carron said in an interview. “It took us 3 years to find the 60 patients” enrolled in CRESPA. “Most of the time, patients go elsewhere for treatment, and it’s several months until they see us. In many countries there are not enough rheumatologists, and patients wait 3, 4 months before we see them.” Another important feature of the intervention was that golimumab treatment continued until patients presented as completely symptom free on two consecutive clinic visits spaced about 12 weeks apart.

Dr. Carron and his associates published their initial findings from CRESPA in 2017 (Ann Rheum Dis. 2017 Aug;76[8]:1389-95), and they also have reported updates on the main results at meetings. At the 2018 EULAR Congress, Dr. Carron reported the outcomes of 31 patients in the study who entered a 2-year period of extended golimumab treatment either because they never reached complete remission or because they relapsed after stopping golimumab and so restarted the drug. Of these patients, 25 completed the full 2 years of the CRESPA extension phase on golimumab. Of those patients, 22 were in complete remission and agreed to continue; they began a tapering phase that started with receiving concurrent treatment with 15 mg/week of oral methotrexate then, after 12 weeks on methotrexate, discontinued their golimumab but continued on the methotrexate regimen.

After an average follow-up of 80 weeks in this postextension phase, 5 patients (23%) remained in remission on methotrexate monotherapy, while the other 17 patients (77%) had to restart golimumab. Of these 17 patients, 15 because of a relapse, and 2 restarted because they had to discontinue methotrexate after developing adverse effects. The median time to restarting golimumab among these 17 patients was 228 days, Dr. Carron said. In all 17 patients, remission returned within 12 weeks of restarting golimumab treatment.

[email protected]

SOURCE: Carron P et al. EULAR 2018 Congress, Abstract OP0335.

AMSTERDAM – Starting patients with newly diagnosed, peripheral spondyloarthritis (SpA) on treatment with a tumor necrosis factor (TNF) inhibitor within 12 weeks of symptom onset produced an “amazing,” long-term, complete remission that resembled cure in more than half of the 40 treated patients, a finding that now needs replication in a larger, multicenter study, Philippe Carron, MD, said at the European Congress of Rheumatology.

Ongoing research on patients in the original study cohort also showed that methotrexate is largely ineffective to help wean patients in remission on a tumor necrosis factor inhibitor off the biologic drug, said Dr. Carron, a rheumatologist at the University of Ghent (Belgium). In his group’s most recent experience with 22 patients in remission on a regimen of golimumab and methotrexate, 5 remained in remission (23%) when golimumab treatment stopped, whereas the other 17 patients had to restart golimumab (Simponi) while continuing on methotrexate after relapsing on methotrexate monotherapy, Dr. Carron reported.

Mitchel L. Zoler/MDedge News

Methotrexate has “overall weak efficacy for maintaining biological-free remission” in patients with peripheral SpA, he concluded.

But Dr. Carron remained very positive about the main finding of the CRESPA (Clinical Remission in Patients with Early Peripheral Spondyloarthritis) study, which has now shown a durable complete remission – free from arthritis, enthesitis, and dactylitis – in 21 of 40 (53%) patients who began golimumab treatment within 12 weeks of their symptom onset and then remained in remission when the golimumab was eventually stopped. These patients have now remained in complete remission for 2.4-5.8 years of follow-up, Dr. Carron said. He attributed this very durable remission while off any treatment to the rapid start of TNF-inhibitor therapy within weeks of their symptom onset.

“This is fantastic; these patients are cured. Early treatment is the most important reason why the result is so good,” but it also poses the biggest challenge for using this approach in routine practice, Dr. Carron said in an interview. “It took us 3 years to find the 60 patients” enrolled in CRESPA. “Most of the time, patients go elsewhere for treatment, and it’s several months until they see us. In many countries there are not enough rheumatologists, and patients wait 3, 4 months before we see them.” Another important feature of the intervention was that golimumab treatment continued until patients presented as completely symptom free on two consecutive clinic visits spaced about 12 weeks apart.

Dr. Carron and his associates published their initial findings from CRESPA in 2017 (Ann Rheum Dis. 2017 Aug;76[8]:1389-95), and they also have reported updates on the main results at meetings. At the 2018 EULAR Congress, Dr. Carron reported the outcomes of 31 patients in the study who entered a 2-year period of extended golimumab treatment either because they never reached complete remission or because they relapsed after stopping golimumab and so restarted the drug. Of these patients, 25 completed the full 2 years of the CRESPA extension phase on golimumab. Of those patients, 22 were in complete remission and agreed to continue; they began a tapering phase that started with receiving concurrent treatment with 15 mg/week of oral methotrexate then, after 12 weeks on methotrexate, discontinued their golimumab but continued on the methotrexate regimen.

After an average follow-up of 80 weeks in this postextension phase, 5 patients (23%) remained in remission on methotrexate monotherapy, while the other 17 patients (77%) had to restart golimumab. Of these 17 patients, 15 because of a relapse, and 2 restarted because they had to discontinue methotrexate after developing adverse effects. The median time to restarting golimumab among these 17 patients was 228 days, Dr. Carron said. In all 17 patients, remission returned within 12 weeks of restarting golimumab treatment.

[email protected]

SOURCE: Carron P et al. EULAR 2018 Congress, Abstract OP0335.

AMSTERDAM – Starting patients with newly diagnosed, peripheral spondyloarthritis (SpA) on treatment with a tumor necrosis factor (TNF) inhibitor within 12 weeks of symptom onset produced an “amazing,” long-term, complete remission that resembled cure in more than half of the 40 treated patients, a finding that now needs replication in a larger, multicenter study, Philippe Carron, MD, said at the European Congress of Rheumatology.

Ongoing research on patients in the original study cohort also showed that methotrexate is largely ineffective to help wean patients in remission on a tumor necrosis factor inhibitor off the biologic drug, said Dr. Carron, a rheumatologist at the University of Ghent (Belgium). In his group’s most recent experience with 22 patients in remission on a regimen of golimumab and methotrexate, 5 remained in remission (23%) when golimumab treatment stopped, whereas the other 17 patients had to restart golimumab (Simponi) while continuing on methotrexate after relapsing on methotrexate monotherapy, Dr. Carron reported.

Mitchel L. Zoler/MDedge News

Methotrexate has “overall weak efficacy for maintaining biological-free remission” in patients with peripheral SpA, he concluded.

But Dr. Carron remained very positive about the main finding of the CRESPA (Clinical Remission in Patients with Early Peripheral Spondyloarthritis) study, which has now shown a durable complete remission – free from arthritis, enthesitis, and dactylitis – in 21 of 40 (53%) patients who began golimumab treatment within 12 weeks of their symptom onset and then remained in remission when the golimumab was eventually stopped. These patients have now remained in complete remission for 2.4-5.8 years of follow-up, Dr. Carron said. He attributed this very durable remission while off any treatment to the rapid start of TNF-inhibitor therapy within weeks of their symptom onset.

“This is fantastic; these patients are cured. Early treatment is the most important reason why the result is so good,” but it also poses the biggest challenge for using this approach in routine practice, Dr. Carron said in an interview. “It took us 3 years to find the 60 patients” enrolled in CRESPA. “Most of the time, patients go elsewhere for treatment, and it’s several months until they see us. In many countries there are not enough rheumatologists, and patients wait 3, 4 months before we see them.” Another important feature of the intervention was that golimumab treatment continued until patients presented as completely symptom free on two consecutive clinic visits spaced about 12 weeks apart.

Dr. Carron and his associates published their initial findings from CRESPA in 2017 (Ann Rheum Dis. 2017 Aug;76[8]:1389-95), and they also have reported updates on the main results at meetings. At the 2018 EULAR Congress, Dr. Carron reported the outcomes of 31 patients in the study who entered a 2-year period of extended golimumab treatment either because they never reached complete remission or because they relapsed after stopping golimumab and so restarted the drug. Of these patients, 25 completed the full 2 years of the CRESPA extension phase on golimumab. Of those patients, 22 were in complete remission and agreed to continue; they began a tapering phase that started with receiving concurrent treatment with 15 mg/week of oral methotrexate then, after 12 weeks on methotrexate, discontinued their golimumab but continued on the methotrexate regimen.

After an average follow-up of 80 weeks in this postextension phase, 5 patients (23%) remained in remission on methotrexate monotherapy, while the other 17 patients (77%) had to restart golimumab. Of these 17 patients, 15 because of a relapse, and 2 restarted because they had to discontinue methotrexate after developing adverse effects. The median time to restarting golimumab among these 17 patients was 228 days, Dr. Carron said. In all 17 patients, remission returned within 12 weeks of restarting golimumab treatment.

[email protected]

SOURCE: Carron P et al. EULAR 2018 Congress, Abstract OP0335.

AMSTERDAM – Treatment with the anti-inflammatory, interleukin-1 blocking drug canakinumab roughly halves gout attacks in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.

While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks, Daniel H. Solomon, MD, said at the European Congress of Rheumatology.

“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.

The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).

It’s also unclear that canakinumab (Ilaris) is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study (N Engl J Med. 2017 Sept 21;377[12]:1119-31). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.

In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.

Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.

[email protected]

SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. Abstract OP0014.

AMSTERDAM – Treatment with the anti-inflammatory, interleukin-1 blocking drug canakinumab roughly halves gout attacks in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.

While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks, Daniel H. Solomon, MD, said at the European Congress of Rheumatology.

“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.

The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).

It’s also unclear that canakinumab (Ilaris) is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study (N Engl J Med. 2017 Sept 21;377[12]:1119-31). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.

In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.

Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.

[email protected]

SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. Abstract OP0014.

AMSTERDAM – Treatment with the anti-inflammatory, interleukin-1 blocking drug canakinumab roughly halves gout attacks in an exploratory, post hoc analysis of data collected from more than 10,000 patients in the CANTOS multicenter, randomized trial.

While this result is only a hypothesis-generating suggestion that blocking interleukin (IL)-1 beta can have a significant impact on the frequency of gout flares, it serves as a proof-of-concept that IL-1 beta blockade is a potentially clinically meaningful strategy for future efforts to block gout attacks, Daniel H. Solomon, MD, said at the European Congress of Rheumatology.

“IL-1 beta is incredibly important in the inflammation associated with gout. Gout is considered by many to be the canonical IL-1 beta disease,” and hence it was important to examine the impact that treatment with the IL-1 beta blocker canakinumab had on gout in the CANTOS trial, Dr. Solomon explained in a video interview.

The answer was that treatment with canakinumab was linked with a roughly 50% reduction in gout flares in the total study group. The same reduction was seen in both the subgroups of patients with and without a history of gout. The effect was seen across all three subgroups of patients, based on their baseline serum urate levels including those with normal, elevated, or very elevated levels and across all the other prespecified subgroups including divisions based on sex, age, baseline body mass index, and baseline level of high-sensitivity C-reactive protein (hsCRP).

It’s also unclear that canakinumab (Ilaris) is the best type of IL-1 beta blocking drug to use for prevention of gout flares. In CANTOS, this expensive drug was administered subcutaneously every 3 months. A more appropriate agent might be an oral, small-molecule drug that blocks IL-1 beta. Several examples of this type of agent are currently in clinical development, said Dr. Solomon, a professor of medicine at Harvard Medical School and a rheumatologist at Brigham and Women’s Hospital, both in Boston.

CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study) randomized 10,061 patients with a history of MI and a hsCRP level of at least 2 mg/L at centers in 39 countries. The study’s primary endpoint was the combined rate of cardiovascular death, MI, or stroke, and canakinumab treatment at the 150-mg dosage level linked with a 15% relative reduction in this endpoint, compared with placebo in this secondary-prevention study (N Engl J Med. 2017 Sept 21;377[12]:1119-31). The study also randomized patients to either of two other canakinumab dosages, 50 mg or 300 mg, administered every 3 months, and, while each of these produced reductions in the primary endpoint relative to placebo, the 150-mg dosage had the largest effect. In the gout analysis reported by Dr. Solomon, the three different canakinumab dosages produced somewhat different levels of gout-flare reductions, but, generally, the effect was similar across the three treatment groups.

In the total study population, regardless of gout history, treatment with 50 mg, 150 mg, and 300 mg canakinumab every 3 months was linked with a reduction in gout attacks of 46%, 57%, and 53%, respectively, compared with placebo-treated patients, Dr. Solomon reported. The three dosages also uniformly produced significantly drops in serum levels of hsCRP, compared with placebo, but canakinumab treatment had no impact on serum urate levels, indicating that the gout-reducing effects of the drug did not occur via a mechanism that involved serum urate.

Because CANTOS exclusively enrolled patients with established coronary disease, the new analysis could not address whether IL-1 beta blockade would also be an effective strategy for reducing gout flares in people without cardiovascular disease, Dr. Solomon cautioned. Although it probably would, he said. He also stressed that treatment with an IL-1 blocking drug should not be seen as a substitute for appropriate urate-lowering treatment in patients with elevated levels of serum urate.

[email protected]

SOURCE: Solomon DH et al. Ann Rheum Dis. 2018;77(Suppl 2):56. Abstract OP0014.

AMSTERDAM – Patients treated with a tumor necrosis factor inhibitor for any indication had their mortality rate cut by about one third, compared with the general population, in a combined analysis of safety findings from 78 trials that involved nearly 30,000 patients.

This first indication that treatment with a tumor necrosis factor inhibitor (TNFi) significantly cut overall mortality only became apparent because of the very large number of patients and patient-years of treatment analyzed, and is likely a real effect – not an artifact – that’s probably linked in part to the anti-inflammatory effect from treatment and its favorable impact on cardiovascular disease events, Gerd R. Burmester, MD, said at the European Congress of Rheumatology.

The cut in overall mortality might also partially result from a “healthy cohort effect,” in which patients enrolled in trials pay more attention to their diet and other aspects of a healthy lifestyle, compared with the general population. But Dr. Burmester cited the recent results from the CANTOS trial that showed treatment with the anti-inflammatory drug canakinumab (Ilaris) was linked with a significant 12% relative reduction in cardiovascular death, myocardial infarction, and stroke (New Engl J Med. 2017 Sept 21;377[12]:1119-31).

“It may be that the anticytokine effect of TNFi works the same way as canakinumab,” Dr. Burmester said in an interview.

The results also confirmed previous reports, based on trial data from fewer numbers of TNFi-treated patients, of low rates of serious infections and malignancies, said Dr. Burmester, professor and director of the department of rheumatology and clinical immunology at Charité Medical University in Berlin.

The data he presented came from both randomized trials and open-label studies of adalimumab (Humira) conducted in several countries worldwide through the end of 2016. The various studies enrolled a total of 29,987 patients treated with adalimumab for 56,951 patient-years who had any of 11 different diseases, including rheumatologic, gastrointestinal, and dermatologic diseases. The most common condition treated in the studies was rheumatoid arthritis (in 33 of the 78 studies), followed by psoriasis (13 studies), and Crohn’s disease (11 studies).

The studies included 9,363 patients treated for at least 2 years, and 4,003 patients treated for at least 5 years. The median duration of adalimumab exposure was 0.7 years and the maximum exposure was just over 12 years.

The overall rate of serious infections in treated patients was 3.7 per 100 patient-years. The most common serious infections were pneumonia, at a rate of 0.6 per 100 patient-years, followed by cellulitis, at a rate of 0.2 per 100 patient-years. Active tuberculosis infections also occurred at a rate of 0.2 per 100 patient-years. Malignancies occurred at a rate of 0.6 per 100 patient-years. These rates were similar to those reported by Dr. Burmester and his associates in 2013 using data from a small pool of patients – 23,458 – enrolled in 71 studies of adalimumab (Ann Rheum Dis. 2013 Apr;72[4]:517-24).

In the current study, Dr. Burmester and his coauthors analyzed the observed mortality rate of the adalimumab-treated patients against the mortality rates for the general populations in the various countries in which the studies were run, based on World Health Organization statistics for the period 1997-2006, and adjusted so that the age and sex of the comparison general populations matched the age and sex of the treated patients. This analysis showed an overall, statistically significant mortality reduction in patients receiving adalimumab of 35%, which was consistent in both the subgroups of men and women.

The observed mortality reduction linked with TNFi treatment is likely a class effect, Dr. Burmester said, although similar analyses have not been conducted using data from patients treated with other TNFis. So far, he has been unsuccessful in getting similar, large-scale trial data from manufacturers of other TNFis that he has approached, but Dr. Burmester said he hopes to eventually receive these data so that he can perform an even larger analysis.

The study was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Burmester has been a consultant to and speaker on behalf of AbbVie, as well as for Bristol Myers Squibb, Merk, Pfizer, Roche, and UCB.

[email protected]

SOURCE: Burmester GR et al. Ann Rheum Dis. 2018;77(Suppl 2):165. Abstract OP0233.

AMSTERDAM – Patients treated with a tumor necrosis factor inhibitor for any indication had their mortality rate cut by about one third, compared with the general population, in a combined analysis of safety findings from 78 trials that involved nearly 30,000 patients.

This first indication that treatment with a tumor necrosis factor inhibitor (TNFi) significantly cut overall mortality only became apparent because of the very large number of patients and patient-years of treatment analyzed, and is likely a real effect – not an artifact – that’s probably linked in part to the anti-inflammatory effect from treatment and its favorable impact on cardiovascular disease events, Gerd R. Burmester, MD, said at the European Congress of Rheumatology.

The cut in overall mortality might also partially result from a “healthy cohort effect,” in which patients enrolled in trials pay more attention to their diet and other aspects of a healthy lifestyle, compared with the general population. But Dr. Burmester cited the recent results from the CANTOS trial that showed treatment with the anti-inflammatory drug canakinumab (Ilaris) was linked with a significant 12% relative reduction in cardiovascular death, myocardial infarction, and stroke (New Engl J Med. 2017 Sept 21;377[12]:1119-31).

“It may be that the anticytokine effect of TNFi works the same way as canakinumab,” Dr. Burmester said in an interview.

The results also confirmed previous reports, based on trial data from fewer numbers of TNFi-treated patients, of low rates of serious infections and malignancies, said Dr. Burmester, professor and director of the department of rheumatology and clinical immunology at Charité Medical University in Berlin.

The data he presented came from both randomized trials and open-label studies of adalimumab (Humira) conducted in several countries worldwide through the end of 2016. The various studies enrolled a total of 29,987 patients treated with adalimumab for 56,951 patient-years who had any of 11 different diseases, including rheumatologic, gastrointestinal, and dermatologic diseases. The most common condition treated in the studies was rheumatoid arthritis (in 33 of the 78 studies), followed by psoriasis (13 studies), and Crohn’s disease (11 studies).

The studies included 9,363 patients treated for at least 2 years, and 4,003 patients treated for at least 5 years. The median duration of adalimumab exposure was 0.7 years and the maximum exposure was just over 12 years.

The overall rate of serious infections in treated patients was 3.7 per 100 patient-years. The most common serious infections were pneumonia, at a rate of 0.6 per 100 patient-years, followed by cellulitis, at a rate of 0.2 per 100 patient-years. Active tuberculosis infections also occurred at a rate of 0.2 per 100 patient-years. Malignancies occurred at a rate of 0.6 per 100 patient-years. These rates were similar to those reported by Dr. Burmester and his associates in 2013 using data from a small pool of patients – 23,458 – enrolled in 71 studies of adalimumab (Ann Rheum Dis. 2013 Apr;72[4]:517-24).

In the current study, Dr. Burmester and his coauthors analyzed the observed mortality rate of the adalimumab-treated patients against the mortality rates for the general populations in the various countries in which the studies were run, based on World Health Organization statistics for the period 1997-2006, and adjusted so that the age and sex of the comparison general populations matched the age and sex of the treated patients. This analysis showed an overall, statistically significant mortality reduction in patients receiving adalimumab of 35%, which was consistent in both the subgroups of men and women.

The observed mortality reduction linked with TNFi treatment is likely a class effect, Dr. Burmester said, although similar analyses have not been conducted using data from patients treated with other TNFis. So far, he has been unsuccessful in getting similar, large-scale trial data from manufacturers of other TNFis that he has approached, but Dr. Burmester said he hopes to eventually receive these data so that he can perform an even larger analysis.

The study was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Burmester has been a consultant to and speaker on behalf of AbbVie, as well as for Bristol Myers Squibb, Merk, Pfizer, Roche, and UCB.

[email protected]

SOURCE: Burmester GR et al. Ann Rheum Dis. 2018;77(Suppl 2):165. Abstract OP0233.

AMSTERDAM – Patients treated with a tumor necrosis factor inhibitor for any indication had their mortality rate cut by about one third, compared with the general population, in a combined analysis of safety findings from 78 trials that involved nearly 30,000 patients.

This first indication that treatment with a tumor necrosis factor inhibitor (TNFi) significantly cut overall mortality only became apparent because of the very large number of patients and patient-years of treatment analyzed, and is likely a real effect – not an artifact – that’s probably linked in part to the anti-inflammatory effect from treatment and its favorable impact on cardiovascular disease events, Gerd R. Burmester, MD, said at the European Congress of Rheumatology.

The cut in overall mortality might also partially result from a “healthy cohort effect,” in which patients enrolled in trials pay more attention to their diet and other aspects of a healthy lifestyle, compared with the general population. But Dr. Burmester cited the recent results from the CANTOS trial that showed treatment with the anti-inflammatory drug canakinumab (Ilaris) was linked with a significant 12% relative reduction in cardiovascular death, myocardial infarction, and stroke (New Engl J Med. 2017 Sept 21;377[12]:1119-31).

“It may be that the anticytokine effect of TNFi works the same way as canakinumab,” Dr. Burmester said in an interview.

The results also confirmed previous reports, based on trial data from fewer numbers of TNFi-treated patients, of low rates of serious infections and malignancies, said Dr. Burmester, professor and director of the department of rheumatology and clinical immunology at Charité Medical University in Berlin.

The data he presented came from both randomized trials and open-label studies of adalimumab (Humira) conducted in several countries worldwide through the end of 2016. The various studies enrolled a total of 29,987 patients treated with adalimumab for 56,951 patient-years who had any of 11 different diseases, including rheumatologic, gastrointestinal, and dermatologic diseases. The most common condition treated in the studies was rheumatoid arthritis (in 33 of the 78 studies), followed by psoriasis (13 studies), and Crohn’s disease (11 studies).

The studies included 9,363 patients treated for at least 2 years, and 4,003 patients treated for at least 5 years. The median duration of adalimumab exposure was 0.7 years and the maximum exposure was just over 12 years.

The overall rate of serious infections in treated patients was 3.7 per 100 patient-years. The most common serious infections were pneumonia, at a rate of 0.6 per 100 patient-years, followed by cellulitis, at a rate of 0.2 per 100 patient-years. Active tuberculosis infections also occurred at a rate of 0.2 per 100 patient-years. Malignancies occurred at a rate of 0.6 per 100 patient-years. These rates were similar to those reported by Dr. Burmester and his associates in 2013 using data from a small pool of patients – 23,458 – enrolled in 71 studies of adalimumab (Ann Rheum Dis. 2013 Apr;72[4]:517-24).

In the current study, Dr. Burmester and his coauthors analyzed the observed mortality rate of the adalimumab-treated patients against the mortality rates for the general populations in the various countries in which the studies were run, based on World Health Organization statistics for the period 1997-2006, and adjusted so that the age and sex of the comparison general populations matched the age and sex of the treated patients. This analysis showed an overall, statistically significant mortality reduction in patients receiving adalimumab of 35%, which was consistent in both the subgroups of men and women.

The observed mortality reduction linked with TNFi treatment is likely a class effect, Dr. Burmester said, although similar analyses have not been conducted using data from patients treated with other TNFis. So far, he has been unsuccessful in getting similar, large-scale trial data from manufacturers of other TNFis that he has approached, but Dr. Burmester said he hopes to eventually receive these data so that he can perform an even larger analysis.

The study was sponsored by AbbVie, the company that markets adalimumab (Humira). Dr. Burmester has been a consultant to and speaker on behalf of AbbVie, as well as for Bristol Myers Squibb, Merk, Pfizer, Roche, and UCB.

[email protected]

SOURCE: Burmester GR et al. Ann Rheum Dis. 2018;77(Suppl 2):165. Abstract OP0233.

AMSTERDAM – Low blood levels of vitamin D were linked with a roughly doubled risk for deep vein thrombosis in a review of nearly 1,400 patients with systemic lupus erythematosus at one U.S. center.

Based on these findings, patients with systemic lupus erythematosus (SLE) should have their blood vitamin D monitored regularly, and if it’s less than 40 ng/mL – the level that was linked with this thrombotic risk – they should receive a vitamin D supplement, Michelle A. Petri, MD, said while presenting a poster at the European Congress of Rheumatology.

She recommended supplementation that provides 50,000 IU of vitamin D weekly, a treatment that appears safe to add to two other routine treatments she recommends for SLE patients – aspirin and hydroxychloroquine.

[email protected]

SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):388, Abstract THU0341.

AMSTERDAM – Low blood levels of vitamin D were linked with a roughly doubled risk for deep vein thrombosis in a review of nearly 1,400 patients with systemic lupus erythematosus at one U.S. center.

Based on these findings, patients with systemic lupus erythematosus (SLE) should have their blood vitamin D monitored regularly, and if it’s less than 40 ng/mL – the level that was linked with this thrombotic risk – they should receive a vitamin D supplement, Michelle A. Petri, MD, said while presenting a poster at the European Congress of Rheumatology.

She recommended supplementation that provides 50,000 IU of vitamin D weekly, a treatment that appears safe to add to two other routine treatments she recommends for SLE patients – aspirin and hydroxychloroquine.

[email protected]

SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):388, Abstract THU0341.

AMSTERDAM – Low blood levels of vitamin D were linked with a roughly doubled risk for deep vein thrombosis in a review of nearly 1,400 patients with systemic lupus erythematosus at one U.S. center.

Based on these findings, patients with systemic lupus erythematosus (SLE) should have their blood vitamin D monitored regularly, and if it’s less than 40 ng/mL – the level that was linked with this thrombotic risk – they should receive a vitamin D supplement, Michelle A. Petri, MD, said while presenting a poster at the European Congress of Rheumatology.

She recommended supplementation that provides 50,000 IU of vitamin D weekly, a treatment that appears safe to add to two other routine treatments she recommends for SLE patients – aspirin and hydroxychloroquine.

[email protected]

SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):388, Abstract THU0341.

WASHINGTON – Less than a quarter of patients with heartburn that appears refractory to proton pump inhibitor treatment truly have reflux-related, drug-refractory heartburn with a high symptom–related probability, but patients who fall into this select subgroup often have significant symptom relief from surgical fundoplication, based on results from a randomized, multicenter, Department of Veterans Affairs study with 78 patients.

Although laparoscopic Nissen fundoplication relieved the heartburn symptoms of just two-thirds of patients who met the study’s definition of having true proton pump inhibitor (PPI)–refractory heartburn, this level of efficacy far exceeded the impact of drug therapy with baclofen or desipramine, which was little better than placebo, Stuart J. Spechler, MD, said at the annual Digestive Disease Week^®.

Mitchel L. Zoler/MDedge News

“Fundoplication fell out of favor because of the success of PPI treatment, and because of complications from the surgery, but what our results show is that there is a subgroup of patients who can benefit from fundoplication. The challenge is identifying them,” said Dr. Spechler, a gastroenterologist and professor of medicine at the University of Texas, Dallas. “If you go through a careful work-up you will find the patients who have true PPI-refractory acid reflux and heartburn, and in the end we don’t have good medical treatments for these patients,” leaving fundoplication as their best hope for symptom relief.

The study he ran included 366 patients seen at about 30 VA Medical Centers across the United States who had been referred to his center because of presumed PPI-refractory heartburn. The careful work-up that Dr. Spechler and his associates ran included a closely supervised, 2-week trial of a standardized PPI regimen with omeprazole, careful symptom scoring on this treatment with a reflux-specific, health-related quality of life questionnaire, endoscopic esophageal manometry, and esophageal pH monitoring while on omeprazole.

This process placed patients into several distinct subgroups: About 19% dropped out of the study during this assessment, and another 15% left the study because of their intolerance of various stages of the work-up. Nearly 12% of patients wound up being responsive to the PPI regimen, about 6% had organic disorders not related to gastroesophageal reflux disease, and 27% had functional heartburn with a normal level of acid reflux, which left 78 patients (21%) who demonstrated true reflux-related, PPI-refractory heartburn symptoms.

The researchers then randomized this 78-patient subgroup into three treatment arms, with one group of 27 underwent fundoplication surgery. A group of 25 underwent active medical therapy with 20 mg omeprazole b.i.d. plus baclofen, which was started at 5 mg t.i.d. and increased to 20 mg t.i.d. In baclofen-intolerant or nonresponding patients, this treatment was followed up with desipramine, increasing from a starting dosage of 25 mg/day to 100 mg/day. A third group of 26 control patients received active omeprazole at the same dosage but placebo in place of the baclofen and desipramine. These three subgroups showed no statistically significant differences at baseline for all demographic and clinical parameters recorded.

The study’s primary endpoint was the percentage of patients in each treatment arm who had a “successful” outcome, defined as at least a 50% improvement in their gastroesophageal reflux health-related quality of life score (J Gastrointest Surg. 1998 Mar-Apr;2[2]:141-5) after 1 year on treatment, which occurred in 67% of the fundoplication patients, 28% in the active medical arm, and 12% in the control arm. The fundoplication-treated patients had a significantly higher rate of a successful outcome, compared with patients in each of the other two treatment groups, while the success rates among patients in the active medical group and the control group did not differ significantly, Dr. Spechler said.

Dr. Spechler had no disclosures to report.

[email protected]

WASHINGTON – Less than a quarter of patients with heartburn that appears refractory to proton pump inhibitor treatment truly have reflux-related, drug-refractory heartburn with a high symptom–related probability, but patients who fall into this select subgroup often have significant symptom relief from surgical fundoplication, based on results from a randomized, multicenter, Department of Veterans Affairs study with 78 patients.

Although laparoscopic Nissen fundoplication relieved the heartburn symptoms of just two-thirds of patients who met the study’s definition of having true proton pump inhibitor (PPI)–refractory heartburn, this level of efficacy far exceeded the impact of drug therapy with baclofen or desipramine, which was little better than placebo, Stuart J. Spechler, MD, said at the annual Digestive Disease Week^®.

Mitchel L. Zoler/MDedge News

“Fundoplication fell out of favor because of the success of PPI treatment, and because of complications from the surgery, but what our results show is that there is a subgroup of patients who can benefit from fundoplication. The challenge is identifying them,” said Dr. Spechler, a gastroenterologist and professor of medicine at the University of Texas, Dallas. “If you go through a careful work-up you will find the patients who have true PPI-refractory acid reflux and heartburn, and in the end we don’t have good medical treatments for these patients,” leaving fundoplication as their best hope for symptom relief.

The study he ran included 366 patients seen at about 30 VA Medical Centers across the United States who had been referred to his center because of presumed PPI-refractory heartburn. The careful work-up that Dr. Spechler and his associates ran included a closely supervised, 2-week trial of a standardized PPI regimen with omeprazole, careful symptom scoring on this treatment with a reflux-specific, health-related quality of life questionnaire, endoscopic esophageal manometry, and esophageal pH monitoring while on omeprazole.

This process placed patients into several distinct subgroups: About 19% dropped out of the study during this assessment, and another 15% left the study because of their intolerance of various stages of the work-up. Nearly 12% of patients wound up being responsive to the PPI regimen, about 6% had organic disorders not related to gastroesophageal reflux disease, and 27% had functional heartburn with a normal level of acid reflux, which left 78 patients (21%) who demonstrated true reflux-related, PPI-refractory heartburn symptoms.

The researchers then randomized this 78-patient subgroup into three treatment arms, with one group of 27 underwent fundoplication surgery. A group of 25 underwent active medical therapy with 20 mg omeprazole b.i.d. plus baclofen, which was started at 5 mg t.i.d. and increased to 20 mg t.i.d. In baclofen-intolerant or nonresponding patients, this treatment was followed up with desipramine, increasing from a starting dosage of 25 mg/day to 100 mg/day. A third group of 26 control patients received active omeprazole at the same dosage but placebo in place of the baclofen and desipramine. These three subgroups showed no statistically significant differences at baseline for all demographic and clinical parameters recorded.

The study’s primary endpoint was the percentage of patients in each treatment arm who had a “successful” outcome, defined as at least a 50% improvement in their gastroesophageal reflux health-related quality of life score (J Gastrointest Surg. 1998 Mar-Apr;2[2]:141-5) after 1 year on treatment, which occurred in 67% of the fundoplication patients, 28% in the active medical arm, and 12% in the control arm. The fundoplication-treated patients had a significantly higher rate of a successful outcome, compared with patients in each of the other two treatment groups, while the success rates among patients in the active medical group and the control group did not differ significantly, Dr. Spechler said.

Dr. Spechler had no disclosures to report.

[email protected]

WASHINGTON – Less than a quarter of patients with heartburn that appears refractory to proton pump inhibitor treatment truly have reflux-related, drug-refractory heartburn with a high symptom–related probability, but patients who fall into this select subgroup often have significant symptom relief from surgical fundoplication, based on results from a randomized, multicenter, Department of Veterans Affairs study with 78 patients.

Although laparoscopic Nissen fundoplication relieved the heartburn symptoms of just two-thirds of patients who met the study’s definition of having true proton pump inhibitor (PPI)–refractory heartburn, this level of efficacy far exceeded the impact of drug therapy with baclofen or desipramine, which was little better than placebo, Stuart J. Spechler, MD, said at the annual Digestive Disease Week^®.

Mitchel L. Zoler/MDedge News

“Fundoplication fell out of favor because of the success of PPI treatment, and because of complications from the surgery, but what our results show is that there is a subgroup of patients who can benefit from fundoplication. The challenge is identifying them,” said Dr. Spechler, a gastroenterologist and professor of medicine at the University of Texas, Dallas. “If you go through a careful work-up you will find the patients who have true PPI-refractory acid reflux and heartburn, and in the end we don’t have good medical treatments for these patients,” leaving fundoplication as their best hope for symptom relief.

The study he ran included 366 patients seen at about 30 VA Medical Centers across the United States who had been referred to his center because of presumed PPI-refractory heartburn. The careful work-up that Dr. Spechler and his associates ran included a closely supervised, 2-week trial of a standardized PPI regimen with omeprazole, careful symptom scoring on this treatment with a reflux-specific, health-related quality of life questionnaire, endoscopic esophageal manometry, and esophageal pH monitoring while on omeprazole.

This process placed patients into several distinct subgroups: About 19% dropped out of the study during this assessment, and another 15% left the study because of their intolerance of various stages of the work-up. Nearly 12% of patients wound up being responsive to the PPI regimen, about 6% had organic disorders not related to gastroesophageal reflux disease, and 27% had functional heartburn with a normal level of acid reflux, which left 78 patients (21%) who demonstrated true reflux-related, PPI-refractory heartburn symptoms.

The researchers then randomized this 78-patient subgroup into three treatment arms, with one group of 27 underwent fundoplication surgery. A group of 25 underwent active medical therapy with 20 mg omeprazole b.i.d. plus baclofen, which was started at 5 mg t.i.d. and increased to 20 mg t.i.d. In baclofen-intolerant or nonresponding patients, this treatment was followed up with desipramine, increasing from a starting dosage of 25 mg/day to 100 mg/day. A third group of 26 control patients received active omeprazole at the same dosage but placebo in place of the baclofen and desipramine. These three subgroups showed no statistically significant differences at baseline for all demographic and clinical parameters recorded.

The study’s primary endpoint was the percentage of patients in each treatment arm who had a “successful” outcome, defined as at least a 50% improvement in their gastroesophageal reflux health-related quality of life score (J Gastrointest Surg. 1998 Mar-Apr;2[2]:141-5) after 1 year on treatment, which occurred in 67% of the fundoplication patients, 28% in the active medical arm, and 12% in the control arm. The fundoplication-treated patients had a significantly higher rate of a successful outcome, compared with patients in each of the other two treatment groups, while the success rates among patients in the active medical group and the control group did not differ significantly, Dr. Spechler said.

Dr. Spechler had no disclosures to report.

[email protected]