Mitchel L. Zoler, PhD

 

AMSTERDAM – The Lupus Low Disease Activity State measure of treatment response offers clinicians an attainable target for patients with systemic lupus erythematosus that correlates with a substantially reduced rate of organ damage, based on a retrospective assessment of data collected from more than 2,000 lupus patients at a single U.S. center.

The analysis showed that when patients with systemic lupus erythematosus (SLE) met the Lupus Low Disease Activity State (LLDAS) criteria at least half the time while on treatment, their overall rate of organ damage was reduced by 52%, compared with patients who never achieved LLDAS, Michelle A. Petri, MD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/MDedge News

Fulfilling the LLDAS criteria more than half the time “is an easier goal to achieve” than other measures of SLE activity, and “more realistic” as a treatment target for both clinical trials as well as in routine practice, said Dr. Petri, professor of medicine and director of the Lupus Center at Johns Hopkins University, Baltimore.

“LLDAS is something that anyone can use in practice,” and has the advantage of including a low steroid dose – no more than 7.5 mg prednisolone/day or an equivalent steroid – as one of its criteria, “a major bad actor” for SLE patients, Dr. Petri said in an interview. LLDAS “is absolutely ready for routine use,” although until now few clinicians have used it to monitor SLE patients, she noted.

“The LLDAS can be a useful target,” commented Ian N. Bruce, MD, professor of rheumatology at the University of Manchester (England), adding that the steroid dosage an SLE patient receives “is an important parameter to measure when assessing an SLE patient.

“It’s not far from being ready for routine use, but I’d like to see more evidence” that it’s a meaningful measure of an SLE patient’s disease status, he said in an interview.

To examine the clinical relevance of the LLDAS criteria, a five-point assessment for SLE first introduced in a 2016 report (Ann Rheum Dis. 2016 Sept;75[9]:1615-21), Dr. Petri and her associates applied it retrospectively to their records for 2,026 SLE patients in a Johns Hopkins registry. Clinicians at Johns Hopkins routinely assessed their SLE patients every 3 months and followed the patients for a median of about 10 years, and so had data from more than 81,000 patient encounters. The researchers used the longitudinal follow-up records to calculate an area under the curve for each patient that tracked their LLDAS state over time. This showed a clear dose-response relationship: The more time an SLE patient spent in LLDAS, the less organ damage they had. Patients who remained in LLDAS at least 75% of the time had a 60% reduction in cumulative organ damage, compared with patients who never achieved LLDAS, Dr. Petri said. The analysis also showed that LLDAS was substantially easier for patients to achieve than the Definitions of Remission in SLE (Ann Rheum Dis. 2017 March;76[3]:554-61). The Johns Hopkins cohort met the LLDAS definition about three times more often than they met the Definitions of Remission in SLE criteria, Dr. Petri said.

The new analysis also showed that LLDAS was especially effective in correlating with statistically significant reductions in future strokes, MI, and end-stage renal disease, though it did not significantly correlate with subsequent reductions in the incidence of cognitive impairment, deep vein thrombosis, malignancy, pulmonary fibrosis, pulmonary hypertension, or cataract development. But the strong correlation of time in LLDAS and the future rate of stroke, MI, or end-stage renal disease was very meaningful because those are the most important types of damage associated with SLE, Dr. Petri said. “LLDAS is a good treatment target as a surrogate” for future risk of SLE complications.

The study had no commercial funding, and Dr. Petri had no disclosures to report. Dr. Bruce has been a consultant to and speaker for GlaxoSmithKline, MedImmune, Pfizer, Roche, and UCB, and he has received research support from Genzyme, GlaxoSmithKline, Human Genome Sciences, Roche, and UCB.

[email protected]

SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):111. Abstract OP0122.

 

AMSTERDAM – The Lupus Low Disease Activity State measure of treatment response offers clinicians an attainable target for patients with systemic lupus erythematosus that correlates with a substantially reduced rate of organ damage, based on a retrospective assessment of data collected from more than 2,000 lupus patients at a single U.S. center.

The analysis showed that when patients with systemic lupus erythematosus (SLE) met the Lupus Low Disease Activity State (LLDAS) criteria at least half the time while on treatment, their overall rate of organ damage was reduced by 52%, compared with patients who never achieved LLDAS, Michelle A. Petri, MD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/MDedge News

Fulfilling the LLDAS criteria more than half the time “is an easier goal to achieve” than other measures of SLE activity, and “more realistic” as a treatment target for both clinical trials as well as in routine practice, said Dr. Petri, professor of medicine and director of the Lupus Center at Johns Hopkins University, Baltimore.

“LLDAS is something that anyone can use in practice,” and has the advantage of including a low steroid dose – no more than 7.5 mg prednisolone/day or an equivalent steroid – as one of its criteria, “a major bad actor” for SLE patients, Dr. Petri said in an interview. LLDAS “is absolutely ready for routine use,” although until now few clinicians have used it to monitor SLE patients, she noted.

“The LLDAS can be a useful target,” commented Ian N. Bruce, MD, professor of rheumatology at the University of Manchester (England), adding that the steroid dosage an SLE patient receives “is an important parameter to measure when assessing an SLE patient.

“It’s not far from being ready for routine use, but I’d like to see more evidence” that it’s a meaningful measure of an SLE patient’s disease status, he said in an interview.

To examine the clinical relevance of the LLDAS criteria, a five-point assessment for SLE first introduced in a 2016 report (Ann Rheum Dis. 2016 Sept;75[9]:1615-21), Dr. Petri and her associates applied it retrospectively to their records for 2,026 SLE patients in a Johns Hopkins registry. Clinicians at Johns Hopkins routinely assessed their SLE patients every 3 months and followed the patients for a median of about 10 years, and so had data from more than 81,000 patient encounters. The researchers used the longitudinal follow-up records to calculate an area under the curve for each patient that tracked their LLDAS state over time. This showed a clear dose-response relationship: The more time an SLE patient spent in LLDAS, the less organ damage they had. Patients who remained in LLDAS at least 75% of the time had a 60% reduction in cumulative organ damage, compared with patients who never achieved LLDAS, Dr. Petri said. The analysis also showed that LLDAS was substantially easier for patients to achieve than the Definitions of Remission in SLE (Ann Rheum Dis. 2017 March;76[3]:554-61). The Johns Hopkins cohort met the LLDAS definition about three times more often than they met the Definitions of Remission in SLE criteria, Dr. Petri said.

The new analysis also showed that LLDAS was especially effective in correlating with statistically significant reductions in future strokes, MI, and end-stage renal disease, though it did not significantly correlate with subsequent reductions in the incidence of cognitive impairment, deep vein thrombosis, malignancy, pulmonary fibrosis, pulmonary hypertension, or cataract development. But the strong correlation of time in LLDAS and the future rate of stroke, MI, or end-stage renal disease was very meaningful because those are the most important types of damage associated with SLE, Dr. Petri said. “LLDAS is a good treatment target as a surrogate” for future risk of SLE complications.

The study had no commercial funding, and Dr. Petri had no disclosures to report. Dr. Bruce has been a consultant to and speaker for GlaxoSmithKline, MedImmune, Pfizer, Roche, and UCB, and he has received research support from Genzyme, GlaxoSmithKline, Human Genome Sciences, Roche, and UCB.

[email protected]

SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):111. Abstract OP0122.

 

AMSTERDAM – The Lupus Low Disease Activity State measure of treatment response offers clinicians an attainable target for patients with systemic lupus erythematosus that correlates with a substantially reduced rate of organ damage, based on a retrospective assessment of data collected from more than 2,000 lupus patients at a single U.S. center.

The analysis showed that when patients with systemic lupus erythematosus (SLE) met the Lupus Low Disease Activity State (LLDAS) criteria at least half the time while on treatment, their overall rate of organ damage was reduced by 52%, compared with patients who never achieved LLDAS, Michelle A. Petri, MD, said at the European Congress of Rheumatology.

Mitchel L. Zoler/MDedge News

Fulfilling the LLDAS criteria more than half the time “is an easier goal to achieve” than other measures of SLE activity, and “more realistic” as a treatment target for both clinical trials as well as in routine practice, said Dr. Petri, professor of medicine and director of the Lupus Center at Johns Hopkins University, Baltimore.

“LLDAS is something that anyone can use in practice,” and has the advantage of including a low steroid dose – no more than 7.5 mg prednisolone/day or an equivalent steroid – as one of its criteria, “a major bad actor” for SLE patients, Dr. Petri said in an interview. LLDAS “is absolutely ready for routine use,” although until now few clinicians have used it to monitor SLE patients, she noted.

“The LLDAS can be a useful target,” commented Ian N. Bruce, MD, professor of rheumatology at the University of Manchester (England), adding that the steroid dosage an SLE patient receives “is an important parameter to measure when assessing an SLE patient.

“It’s not far from being ready for routine use, but I’d like to see more evidence” that it’s a meaningful measure of an SLE patient’s disease status, he said in an interview.

To examine the clinical relevance of the LLDAS criteria, a five-point assessment for SLE first introduced in a 2016 report (Ann Rheum Dis. 2016 Sept;75[9]:1615-21), Dr. Petri and her associates applied it retrospectively to their records for 2,026 SLE patients in a Johns Hopkins registry. Clinicians at Johns Hopkins routinely assessed their SLE patients every 3 months and followed the patients for a median of about 10 years, and so had data from more than 81,000 patient encounters. The researchers used the longitudinal follow-up records to calculate an area under the curve for each patient that tracked their LLDAS state over time. This showed a clear dose-response relationship: The more time an SLE patient spent in LLDAS, the less organ damage they had. Patients who remained in LLDAS at least 75% of the time had a 60% reduction in cumulative organ damage, compared with patients who never achieved LLDAS, Dr. Petri said. The analysis also showed that LLDAS was substantially easier for patients to achieve than the Definitions of Remission in SLE (Ann Rheum Dis. 2017 March;76[3]:554-61). The Johns Hopkins cohort met the LLDAS definition about three times more often than they met the Definitions of Remission in SLE criteria, Dr. Petri said.

The new analysis also showed that LLDAS was especially effective in correlating with statistically significant reductions in future strokes, MI, and end-stage renal disease, though it did not significantly correlate with subsequent reductions in the incidence of cognitive impairment, deep vein thrombosis, malignancy, pulmonary fibrosis, pulmonary hypertension, or cataract development. But the strong correlation of time in LLDAS and the future rate of stroke, MI, or end-stage renal disease was very meaningful because those are the most important types of damage associated with SLE, Dr. Petri said. “LLDAS is a good treatment target as a surrogate” for future risk of SLE complications.

The study had no commercial funding, and Dr. Petri had no disclosures to report. Dr. Bruce has been a consultant to and speaker for GlaxoSmithKline, MedImmune, Pfizer, Roche, and UCB, and he has received research support from Genzyme, GlaxoSmithKline, Human Genome Sciences, Roche, and UCB.

[email protected]

SOURCE: Petri MA et al. Ann Rheum Dis. 2018;77(Suppl 2):111. Abstract OP0122.

 

AMSTERDAM – Older women on bisphosphonate treatment for at least 3 years who then stopped taking the drug showed a 40% increased risk for hip fracture after they were off the bisphosphonate for more than 2 years, compared with women who never stopped using the drug, according to an analysis of more than 150,000 women in a Medicare database.

The implication of this observational-data finding is that drug holidays from a bisphosphonate regimen “may not be appropriate for all patients,” Kenneth G. Saag, MD, said at the European Congress of Rheumatology.

The finding seems to dispute a recent recommendation from the American College of Physicians (Ann Intern Med. 2017 June 6;166[11]:818-39) that drug treatment to prevent bone fractures in osteoporotic women should stop after 5 years, noted Dr. Saag, a rheumatologist and professor of medicine at the University of Alabama, Birmingham. The median duration of bisphosphonate treatment in the studied cohort before the drug use stopped was 5.5 years.

“Drug holidays [from a bisphosphonate] have become increasingly common” because of concerns about potential adverse effects from prolonged, continuous bisphosphonate treatment, especially the risk for osteonecrosis of the jaw and atypical femoral fractures, he said. These bisphosphonate stoppages are sometimes permanent and sometimes temporary, Dr. Saag noted. Ideally, assessment of the risks and benefits from a bisphosphonate drug holiday should occur in a randomized study, but in current U.S. practice such a trial would be “impossible because there is not equipoise around the decision of whether or not to stop,” he said.

Mitchel L. Zoler/MDedge News

To try to gain insight into the impact of halting bisphosphonate treatment with observational data, Dr. Saag and his associates used records collected by Medicare on 153,236 women who started a new course of bisphosphonate treatment and remained on it for at least 3 years during 2006 to 2014. When selecting these women, the researchers also focused on those with at least 80% adherence to their bisphosphonate regimen, based on prescription coverage data. The analysis censored women who also received other treatments that can affect bone density, such as estrogen or denosumab (Prolia, Xgeva). The average age of the women was 79 years; two-thirds were aged 75 years or older. The median duration of follow-up information after bisphosphonate stoppage was 2.1 years. Forty percent of the women stopped their bisphosphonate treatment for at least 6 months, and 13% of the women who stopped treatment subsequently restarted a bisphosphonate drug. The most commonly used bisphosphonate was alendronate (Fosamax, Binosto), used by 72%, followed by zoledronic acid (Reclast, Zometa), used by 16%.

The analysis divided women who stopped their bisphosphonate treatment into subgroups based on the duration of stoppage, and showed that the rate of hip fracture was 40% higher among women who stopped treatment for more than 2 years but not more than 3 years, compared with the women who never interrupted their bisphosphonate treatment, a statistically significant difference, Dr. Saag said. In contrast, among women who halted bisphosphonate treatment for more than 1 year but not more than 2 years, the hip fracture risk was 20% higher than that of nonstoppers, also a statistically significant difference. These and all the other analyses the researchers ran adjusted for the possible impact from baseline differences in several demographic and clinical variables.

Dr. Saag cautioned that while the relatively increased risk for hip fracture from a prolonged halt to bisphosphonate treatment was 40%, the absolute increase in risk was “relatively modest,” representing an increased fracture rate of 0.5-1 additional fractures during every 100 patient years of follow-up.

For the endpoint of major osteoporotic fracture at any location, the risk was 10% higher among women who stopped treatment for more than 2 years but not for longer than 3 years, compared with nonstoppers.

The researchers also focused on two key subgroups. Among women who only took alendronate, a drug holiday of more than 2 years was linked with a statistically significant 20% rise in hip fractures, compared with women who never stopped the drug. And among the 4% of studied women who had a history of a bone fracture because of bone fragility, stoppage of their bisphosphonate treatment for more than 2 years doubled their hip fracture rate, compared with similar women who did not stop their treatment.

The study received no commercial funding. Dr. Saag has been a consultant to and has received research funding from Amgen, Lilly, and Radius.

[email protected]

SOURCE: Curtis J et al. EULAR 2018 Congress, abstract OP0017.

 

AMSTERDAM – Older women on bisphosphonate treatment for at least 3 years who then stopped taking the drug showed a 40% increased risk for hip fracture after they were off the bisphosphonate for more than 2 years, compared with women who never stopped using the drug, according to an analysis of more than 150,000 women in a Medicare database.

The implication of this observational-data finding is that drug holidays from a bisphosphonate regimen “may not be appropriate for all patients,” Kenneth G. Saag, MD, said at the European Congress of Rheumatology.

The finding seems to dispute a recent recommendation from the American College of Physicians (Ann Intern Med. 2017 June 6;166[11]:818-39) that drug treatment to prevent bone fractures in osteoporotic women should stop after 5 years, noted Dr. Saag, a rheumatologist and professor of medicine at the University of Alabama, Birmingham. The median duration of bisphosphonate treatment in the studied cohort before the drug use stopped was 5.5 years.

“Drug holidays [from a bisphosphonate] have become increasingly common” because of concerns about potential adverse effects from prolonged, continuous bisphosphonate treatment, especially the risk for osteonecrosis of the jaw and atypical femoral fractures, he said. These bisphosphonate stoppages are sometimes permanent and sometimes temporary, Dr. Saag noted. Ideally, assessment of the risks and benefits from a bisphosphonate drug holiday should occur in a randomized study, but in current U.S. practice such a trial would be “impossible because there is not equipoise around the decision of whether or not to stop,” he said.

Mitchel L. Zoler/MDedge News

To try to gain insight into the impact of halting bisphosphonate treatment with observational data, Dr. Saag and his associates used records collected by Medicare on 153,236 women who started a new course of bisphosphonate treatment and remained on it for at least 3 years during 2006 to 2014. When selecting these women, the researchers also focused on those with at least 80% adherence to their bisphosphonate regimen, based on prescription coverage data. The analysis censored women who also received other treatments that can affect bone density, such as estrogen or denosumab (Prolia, Xgeva). The average age of the women was 79 years; two-thirds were aged 75 years or older. The median duration of follow-up information after bisphosphonate stoppage was 2.1 years. Forty percent of the women stopped their bisphosphonate treatment for at least 6 months, and 13% of the women who stopped treatment subsequently restarted a bisphosphonate drug. The most commonly used bisphosphonate was alendronate (Fosamax, Binosto), used by 72%, followed by zoledronic acid (Reclast, Zometa), used by 16%.

The analysis divided women who stopped their bisphosphonate treatment into subgroups based on the duration of stoppage, and showed that the rate of hip fracture was 40% higher among women who stopped treatment for more than 2 years but not more than 3 years, compared with the women who never interrupted their bisphosphonate treatment, a statistically significant difference, Dr. Saag said. In contrast, among women who halted bisphosphonate treatment for more than 1 year but not more than 2 years, the hip fracture risk was 20% higher than that of nonstoppers, also a statistically significant difference. These and all the other analyses the researchers ran adjusted for the possible impact from baseline differences in several demographic and clinical variables.

Dr. Saag cautioned that while the relatively increased risk for hip fracture from a prolonged halt to bisphosphonate treatment was 40%, the absolute increase in risk was “relatively modest,” representing an increased fracture rate of 0.5-1 additional fractures during every 100 patient years of follow-up.

For the endpoint of major osteoporotic fracture at any location, the risk was 10% higher among women who stopped treatment for more than 2 years but not for longer than 3 years, compared with nonstoppers.

The researchers also focused on two key subgroups. Among women who only took alendronate, a drug holiday of more than 2 years was linked with a statistically significant 20% rise in hip fractures, compared with women who never stopped the drug. And among the 4% of studied women who had a history of a bone fracture because of bone fragility, stoppage of their bisphosphonate treatment for more than 2 years doubled their hip fracture rate, compared with similar women who did not stop their treatment.

The study received no commercial funding. Dr. Saag has been a consultant to and has received research funding from Amgen, Lilly, and Radius.

[email protected]

SOURCE: Curtis J et al. EULAR 2018 Congress, abstract OP0017.

 

AMSTERDAM – Older women on bisphosphonate treatment for at least 3 years who then stopped taking the drug showed a 40% increased risk for hip fracture after they were off the bisphosphonate for more than 2 years, compared with women who never stopped using the drug, according to an analysis of more than 150,000 women in a Medicare database.

The implication of this observational-data finding is that drug holidays from a bisphosphonate regimen “may not be appropriate for all patients,” Kenneth G. Saag, MD, said at the European Congress of Rheumatology.

The finding seems to dispute a recent recommendation from the American College of Physicians (Ann Intern Med. 2017 June 6;166[11]:818-39) that drug treatment to prevent bone fractures in osteoporotic women should stop after 5 years, noted Dr. Saag, a rheumatologist and professor of medicine at the University of Alabama, Birmingham. The median duration of bisphosphonate treatment in the studied cohort before the drug use stopped was 5.5 years.

“Drug holidays [from a bisphosphonate] have become increasingly common” because of concerns about potential adverse effects from prolonged, continuous bisphosphonate treatment, especially the risk for osteonecrosis of the jaw and atypical femoral fractures, he said. These bisphosphonate stoppages are sometimes permanent and sometimes temporary, Dr. Saag noted. Ideally, assessment of the risks and benefits from a bisphosphonate drug holiday should occur in a randomized study, but in current U.S. practice such a trial would be “impossible because there is not equipoise around the decision of whether or not to stop,” he said.

Mitchel L. Zoler/MDedge News

To try to gain insight into the impact of halting bisphosphonate treatment with observational data, Dr. Saag and his associates used records collected by Medicare on 153,236 women who started a new course of bisphosphonate treatment and remained on it for at least 3 years during 2006 to 2014. When selecting these women, the researchers also focused on those with at least 80% adherence to their bisphosphonate regimen, based on prescription coverage data. The analysis censored women who also received other treatments that can affect bone density, such as estrogen or denosumab (Prolia, Xgeva). The average age of the women was 79 years; two-thirds were aged 75 years or older. The median duration of follow-up information after bisphosphonate stoppage was 2.1 years. Forty percent of the women stopped their bisphosphonate treatment for at least 6 months, and 13% of the women who stopped treatment subsequently restarted a bisphosphonate drug. The most commonly used bisphosphonate was alendronate (Fosamax, Binosto), used by 72%, followed by zoledronic acid (Reclast, Zometa), used by 16%.

The analysis divided women who stopped their bisphosphonate treatment into subgroups based on the duration of stoppage, and showed that the rate of hip fracture was 40% higher among women who stopped treatment for more than 2 years but not more than 3 years, compared with the women who never interrupted their bisphosphonate treatment, a statistically significant difference, Dr. Saag said. In contrast, among women who halted bisphosphonate treatment for more than 1 year but not more than 2 years, the hip fracture risk was 20% higher than that of nonstoppers, also a statistically significant difference. These and all the other analyses the researchers ran adjusted for the possible impact from baseline differences in several demographic and clinical variables.

Dr. Saag cautioned that while the relatively increased risk for hip fracture from a prolonged halt to bisphosphonate treatment was 40%, the absolute increase in risk was “relatively modest,” representing an increased fracture rate of 0.5-1 additional fractures during every 100 patient years of follow-up.

For the endpoint of major osteoporotic fracture at any location, the risk was 10% higher among women who stopped treatment for more than 2 years but not for longer than 3 years, compared with nonstoppers.

The researchers also focused on two key subgroups. Among women who only took alendronate, a drug holiday of more than 2 years was linked with a statistically significant 20% rise in hip fractures, compared with women who never stopped the drug. And among the 4% of studied women who had a history of a bone fracture because of bone fragility, stoppage of their bisphosphonate treatment for more than 2 years doubled their hip fracture rate, compared with similar women who did not stop their treatment.

The study received no commercial funding. Dr. Saag has been a consultant to and has received research funding from Amgen, Lilly, and Radius.

[email protected]

SOURCE: Curtis J et al. EULAR 2018 Congress, abstract OP0017.

WASHINGTON – Using hemostatic clips to close colonic mucosal defects following endoscopic removal of larger polyps cut the rate of delayed, severe bleeding episodes in half in a multicenter, randomized trial with 918 patients.

“The benefit appears limited to proximal polyps,” Heiko Pohl, MD, said at the annual Digestive Disease Week^®. In that prespecified subgroup, which included two-thirds of enrolled patients, placement of hemostatic clips on defects left after removing polyps 20 mm in diameter or larger cut the rate of delayed, severe bleeding by two-thirds, compared with patients with large defects not treated with clips. This result represented a number needed to treat with clips of 15 patients with large proximal polyps to prevent one episode of delayed severe bleeding, said Dr. Pohl, a gastroenterologist at the VA Medical Center in White River Junction, Vt.

Mitchel L. Zoler/MDedge News

Although the results that Dr. Pohl reported came from a trial that originally had been designed to generate data for Food and Drug Administration approval for using the clips to close defects following large polyp removal, the clips received approval for this indication from the agency in 2016 while the study was still in progress.

But Dr. Pohl maintained that the new evidence for efficacy that he reported will provide further impetus for gastroenterologists to use clips when they remove larger polyps in proximal locations. “I think this study will help standardize treatment of mucosal resections and change clip use,” he said in an interview.

“This was a terrific study, and one that needed to be done,” commented John R. Saltzman, MD, professor of medicine at Harvard Medical School and director of endoscopy at Brigham and Women’s Hospital in Boston. But Dr. Saltzman, who spoke from the floor during discussion of Dr. Pohl’s report, added that data on the average number of clips required to close defects were needed to assess the cost-effectiveness of the treatment, data that Dr. Pohl said were available but still being analyzed.

“We have to know how many clips to use and how to close the polyp,” Dr. Saltzman said. Dr. Pohl estimated that roughly four or five clips had been used per defect, but he cautioned that this estimate was preliminary pending his complete analysis of the data.

The CLIP (Clip Closure After Endoscopic Resection of Large Polyps) study enrolled patients with at least one nonpedunculated colonic polyp that was at least 20 mm in diameter at 16 U.S. centers, as well as one center in Montreal and one in Barcelona. The patients averaged 65 years of age, and 6%-7% of patients had more than one large polyp removed during their procedure. Randomization produced one important imbalance in assignment: 25% of the 454 patients in the clipped arm were on an antithrombotic drug (either an anticoagulant or antiplatelet drug) at the time of their endoscopy, compared with 33% of the 464 patients in the control arm.

The study’s primary endpoint was the incidence of “severe” bleeding within 30 days after the procedure. The study defined severe bleeding as an event that required hospitalization, need for repeat endoscopy, need for a blood transfusion, or need for any other major intervention, explained Dr. Pohl, who is also on the staff of Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

Such events occurred in 3.5% of the patients who underwent clipping and in 7.3% of control patients who received no clipping, a statistically significant difference (P = .01). Among patients with proximal polyps, the bleeding rates were 3.3% among clipped patients and 9.9% among controls, also a statistically significant difference. Among patients with distal polyps the bleeding rates were 4.0% among clipped patients and 1.4% among controls, a difference that was not statistically significant.

Dr. Pohl and his associates ran three other prespecified, secondary analyses that divided the enrolled patients into subgroups. These analyses showed no significant effect on outcome by polyp size when comparing 20-39 mm polyps with polyps 40 mm or larger, treatment with an antithrombotic drug, or method of cauterization. The median time to severe bleeding was 1 day among the controls and 7 days among the clipped patients.

Aside from the difference in rates of delayed bleeding, the two study arms showed no significant differences in the incidence of any other serious postprocedure events. The rates of these nonbleeding events were 1.3% among clipped patients and 2.4% among the controls.

The researchers ran all these analyses based on the intention-to-treat assignment of patients. However, during the study, 9% of patients assigned to the control arm crossed over ended up receiving clips during their procedure after all, a rate that Dr. Pohl called “surprisingly high,” whereas 14% of patients assigned to the clip arm never received clips. A per-protocol analysis that censored patients who did not receive their assigned treatment showed that, among the remaining patients who underwent their assigned treatment, the rate of delayed, severe bleeds was 2.3% among the 390 patients actually treated with clips and 7.2% among the 419 controls who never received clips, a statistically significant difference, he reported.

Dr. Pohl also noted that it was “somewhat surprising” that clipping appeared to result in complete closure in “only” 68% of patients who underwent clipping and that it produced partial closure in an additional 20% of patients, with the remaining patients having mucosal defects that were not considered closed by clipping.

The study was funded by Boston Scientific, the company that markets the hemostatic clip (Resolution 360) tested in the study. Dr. Pohl had no additional disclosures. Dr. Saltzman had no disclosures.

[email protected]

SOURCE: Pohl H et al. Digestive Disease Week, Presentation 886.

WASHINGTON – Using hemostatic clips to close colonic mucosal defects following endoscopic removal of larger polyps cut the rate of delayed, severe bleeding episodes in half in a multicenter, randomized trial with 918 patients.

“The benefit appears limited to proximal polyps,” Heiko Pohl, MD, said at the annual Digestive Disease Week^®. In that prespecified subgroup, which included two-thirds of enrolled patients, placement of hemostatic clips on defects left after removing polyps 20 mm in diameter or larger cut the rate of delayed, severe bleeding by two-thirds, compared with patients with large defects not treated with clips. This result represented a number needed to treat with clips of 15 patients with large proximal polyps to prevent one episode of delayed severe bleeding, said Dr. Pohl, a gastroenterologist at the VA Medical Center in White River Junction, Vt.

Mitchel L. Zoler/MDedge News

Although the results that Dr. Pohl reported came from a trial that originally had been designed to generate data for Food and Drug Administration approval for using the clips to close defects following large polyp removal, the clips received approval for this indication from the agency in 2016 while the study was still in progress.

But Dr. Pohl maintained that the new evidence for efficacy that he reported will provide further impetus for gastroenterologists to use clips when they remove larger polyps in proximal locations. “I think this study will help standardize treatment of mucosal resections and change clip use,” he said in an interview.

“This was a terrific study, and one that needed to be done,” commented John R. Saltzman, MD, professor of medicine at Harvard Medical School and director of endoscopy at Brigham and Women’s Hospital in Boston. But Dr. Saltzman, who spoke from the floor during discussion of Dr. Pohl’s report, added that data on the average number of clips required to close defects were needed to assess the cost-effectiveness of the treatment, data that Dr. Pohl said were available but still being analyzed.

“We have to know how many clips to use and how to close the polyp,” Dr. Saltzman said. Dr. Pohl estimated that roughly four or five clips had been used per defect, but he cautioned that this estimate was preliminary pending his complete analysis of the data.

The CLIP (Clip Closure After Endoscopic Resection of Large Polyps) study enrolled patients with at least one nonpedunculated colonic polyp that was at least 20 mm in diameter at 16 U.S. centers, as well as one center in Montreal and one in Barcelona. The patients averaged 65 years of age, and 6%-7% of patients had more than one large polyp removed during their procedure. Randomization produced one important imbalance in assignment: 25% of the 454 patients in the clipped arm were on an antithrombotic drug (either an anticoagulant or antiplatelet drug) at the time of their endoscopy, compared with 33% of the 464 patients in the control arm.

The study’s primary endpoint was the incidence of “severe” bleeding within 30 days after the procedure. The study defined severe bleeding as an event that required hospitalization, need for repeat endoscopy, need for a blood transfusion, or need for any other major intervention, explained Dr. Pohl, who is also on the staff of Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

Such events occurred in 3.5% of the patients who underwent clipping and in 7.3% of control patients who received no clipping, a statistically significant difference (P = .01). Among patients with proximal polyps, the bleeding rates were 3.3% among clipped patients and 9.9% among controls, also a statistically significant difference. Among patients with distal polyps the bleeding rates were 4.0% among clipped patients and 1.4% among controls, a difference that was not statistically significant.

Dr. Pohl and his associates ran three other prespecified, secondary analyses that divided the enrolled patients into subgroups. These analyses showed no significant effect on outcome by polyp size when comparing 20-39 mm polyps with polyps 40 mm or larger, treatment with an antithrombotic drug, or method of cauterization. The median time to severe bleeding was 1 day among the controls and 7 days among the clipped patients.

Aside from the difference in rates of delayed bleeding, the two study arms showed no significant differences in the incidence of any other serious postprocedure events. The rates of these nonbleeding events were 1.3% among clipped patients and 2.4% among the controls.

The researchers ran all these analyses based on the intention-to-treat assignment of patients. However, during the study, 9% of patients assigned to the control arm crossed over ended up receiving clips during their procedure after all, a rate that Dr. Pohl called “surprisingly high,” whereas 14% of patients assigned to the clip arm never received clips. A per-protocol analysis that censored patients who did not receive their assigned treatment showed that, among the remaining patients who underwent their assigned treatment, the rate of delayed, severe bleeds was 2.3% among the 390 patients actually treated with clips and 7.2% among the 419 controls who never received clips, a statistically significant difference, he reported.

Dr. Pohl also noted that it was “somewhat surprising” that clipping appeared to result in complete closure in “only” 68% of patients who underwent clipping and that it produced partial closure in an additional 20% of patients, with the remaining patients having mucosal defects that were not considered closed by clipping.

The study was funded by Boston Scientific, the company that markets the hemostatic clip (Resolution 360) tested in the study. Dr. Pohl had no additional disclosures. Dr. Saltzman had no disclosures.

[email protected]

SOURCE: Pohl H et al. Digestive Disease Week, Presentation 886.

WASHINGTON – Using hemostatic clips to close colonic mucosal defects following endoscopic removal of larger polyps cut the rate of delayed, severe bleeding episodes in half in a multicenter, randomized trial with 918 patients.

“The benefit appears limited to proximal polyps,” Heiko Pohl, MD, said at the annual Digestive Disease Week^®. In that prespecified subgroup, which included two-thirds of enrolled patients, placement of hemostatic clips on defects left after removing polyps 20 mm in diameter or larger cut the rate of delayed, severe bleeding by two-thirds, compared with patients with large defects not treated with clips. This result represented a number needed to treat with clips of 15 patients with large proximal polyps to prevent one episode of delayed severe bleeding, said Dr. Pohl, a gastroenterologist at the VA Medical Center in White River Junction, Vt.

Mitchel L. Zoler/MDedge News

Although the results that Dr. Pohl reported came from a trial that originally had been designed to generate data for Food and Drug Administration approval for using the clips to close defects following large polyp removal, the clips received approval for this indication from the agency in 2016 while the study was still in progress.

But Dr. Pohl maintained that the new evidence for efficacy that he reported will provide further impetus for gastroenterologists to use clips when they remove larger polyps in proximal locations. “I think this study will help standardize treatment of mucosal resections and change clip use,” he said in an interview.

“This was a terrific study, and one that needed to be done,” commented John R. Saltzman, MD, professor of medicine at Harvard Medical School and director of endoscopy at Brigham and Women’s Hospital in Boston. But Dr. Saltzman, who spoke from the floor during discussion of Dr. Pohl’s report, added that data on the average number of clips required to close defects were needed to assess the cost-effectiveness of the treatment, data that Dr. Pohl said were available but still being analyzed.

“We have to know how many clips to use and how to close the polyp,” Dr. Saltzman said. Dr. Pohl estimated that roughly four or five clips had been used per defect, but he cautioned that this estimate was preliminary pending his complete analysis of the data.

The CLIP (Clip Closure After Endoscopic Resection of Large Polyps) study enrolled patients with at least one nonpedunculated colonic polyp that was at least 20 mm in diameter at 16 U.S. centers, as well as one center in Montreal and one in Barcelona. The patients averaged 65 years of age, and 6%-7% of patients had more than one large polyp removed during their procedure. Randomization produced one important imbalance in assignment: 25% of the 454 patients in the clipped arm were on an antithrombotic drug (either an anticoagulant or antiplatelet drug) at the time of their endoscopy, compared with 33% of the 464 patients in the control arm.

The study’s primary endpoint was the incidence of “severe” bleeding within 30 days after the procedure. The study defined severe bleeding as an event that required hospitalization, need for repeat endoscopy, need for a blood transfusion, or need for any other major intervention, explained Dr. Pohl, who is also on the staff of Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

Such events occurred in 3.5% of the patients who underwent clipping and in 7.3% of control patients who received no clipping, a statistically significant difference (P = .01). Among patients with proximal polyps, the bleeding rates were 3.3% among clipped patients and 9.9% among controls, also a statistically significant difference. Among patients with distal polyps the bleeding rates were 4.0% among clipped patients and 1.4% among controls, a difference that was not statistically significant.

Dr. Pohl and his associates ran three other prespecified, secondary analyses that divided the enrolled patients into subgroups. These analyses showed no significant effect on outcome by polyp size when comparing 20-39 mm polyps with polyps 40 mm or larger, treatment with an antithrombotic drug, or method of cauterization. The median time to severe bleeding was 1 day among the controls and 7 days among the clipped patients.

Aside from the difference in rates of delayed bleeding, the two study arms showed no significant differences in the incidence of any other serious postprocedure events. The rates of these nonbleeding events were 1.3% among clipped patients and 2.4% among the controls.

The researchers ran all these analyses based on the intention-to-treat assignment of patients. However, during the study, 9% of patients assigned to the control arm crossed over ended up receiving clips during their procedure after all, a rate that Dr. Pohl called “surprisingly high,” whereas 14% of patients assigned to the clip arm never received clips. A per-protocol analysis that censored patients who did not receive their assigned treatment showed that, among the remaining patients who underwent their assigned treatment, the rate of delayed, severe bleeds was 2.3% among the 390 patients actually treated with clips and 7.2% among the 419 controls who never received clips, a statistically significant difference, he reported.

Dr. Pohl also noted that it was “somewhat surprising” that clipping appeared to result in complete closure in “only” 68% of patients who underwent clipping and that it produced partial closure in an additional 20% of patients, with the remaining patients having mucosal defects that were not considered closed by clipping.

The study was funded by Boston Scientific, the company that markets the hemostatic clip (Resolution 360) tested in the study. Dr. Pohl had no additional disclosures. Dr. Saltzman had no disclosures.

[email protected]

SOURCE: Pohl H et al. Digestive Disease Week, Presentation 886.

 

BOSTON – The direct acting oral anticoagulants boost patient adherence compared with warfarin anticoagulation, but when patients did not adhere to their regimens, those prescribed a new, direct-acting oral anticoagulant had worse outcomes than did patients on warfarin – even patients poorly adherent with warfarin – based on data from more than 80,000 U.S. patients.

Among low-adherence patients, defined as those with adherence rates of 40%-80% based on prescriptions filled, patients with nonvalvular atrial fibrillation and a CHA₂DS₂-VASc score of at least 2 and treated with warfarin had a 3.37/100 patient-years rate of thromboembolic events–driven hospitalizations or emergency department visits, compared with a 4.05/100 patient-years rate among low-adherence patients receiving a direct-acting oral anticoagulant (DOAC), Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. The incidence of strokes of any kind was also lower in the low-adherence warfarin patients compared with the low-adherence DOAC patients, although the relationship flipped for hemorrhagic strokes and bleeds, which were more common in the warfarin patients.

In contrast, when patients were adherent, taking more than 80% of their prescribed drug, the performance of the DOACs generally surpassed that of warfarin. In an analysis adjusted for several demographic and clinical confounders, and when compared with patients adherent to a warfarin regimen, those adherent to a DOAC had a 7% lower rate of thromboembolic events, a 36% lower rate of hemorrhagic strokes, an 8% lower rate of any stroke, and a 10% lower rate of bleeds (excluding hemorrhagic strokes), all statistically significant differences, reported Dr. Lakkireddy, medical director of the Kansas City Heart Rhythm Institute in Overland Park, Kan.

The message from this analysis is the importance of maximizing patient adherence, Dr. Lakkireddy said.

Mitchel L. Zoler/MDedge News

“We should not make the false assumption that putting a patient on a DOAC will take care of everything. We need to make it a habit to make sure patients are taking their pills,” he said in an interview. “We were surprised. Our assumption was that the DOACs were more forgiving than warfarin” in poorly compliant patients. “We need to make talking about adherence with patients routine.”

The results also documented that adherence to therapy is better with a DOAC, with a 74% rate of good adherence among the nearly 41,000 patients in the database prescribed a DOAC compared with a 63% rate of good compliance among the more than 42,000 patients prescribed warfarin.

“It’s ironic that we might think low-adherence patients should go on warfarin. That’s sort of backwards,” said Andrew D. Krahn, MD, a cardiac electrophysiologist and professor of medicine at the University of British Columbia in Vancouver. “It’s not biologically plausible” to predict that less adherent patients would do better on warfarin, he noted.

Mitchel L. Zoler/MDedge News

The study run by Dr. Lakkireddy and his associates used data collected by IBM Watson Health Market Scan from about 4 million Medicare patients and 47 million American residents with private insurance during 2012-2016. They focused on the more than 600,000 patients prescribed an anticoagulant during 2014 and 2015, and then narrowed the study group down to just over 83,000 adults with nonvalvular atrial fibrillation, a CHA₂DS₂-VASc score of 2 or more. The patients’ average age was about 74 years.

Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehringer Ingelheim, Bristol Myers Squibb, EstechPharma, Janssen, Pfizer, SentreHeart, and St. Jude. Dr. Krahn has been a consultant to Medtronic and has received research support from Medtronic and Boston Scientific.

[email protected]

SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-03.

 

BOSTON – The direct acting oral anticoagulants boost patient adherence compared with warfarin anticoagulation, but when patients did not adhere to their regimens, those prescribed a new, direct-acting oral anticoagulant had worse outcomes than did patients on warfarin – even patients poorly adherent with warfarin – based on data from more than 80,000 U.S. patients.

Among low-adherence patients, defined as those with adherence rates of 40%-80% based on prescriptions filled, patients with nonvalvular atrial fibrillation and a CHA₂DS₂-VASc score of at least 2 and treated with warfarin had a 3.37/100 patient-years rate of thromboembolic events–driven hospitalizations or emergency department visits, compared with a 4.05/100 patient-years rate among low-adherence patients receiving a direct-acting oral anticoagulant (DOAC), Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. The incidence of strokes of any kind was also lower in the low-adherence warfarin patients compared with the low-adherence DOAC patients, although the relationship flipped for hemorrhagic strokes and bleeds, which were more common in the warfarin patients.

In contrast, when patients were adherent, taking more than 80% of their prescribed drug, the performance of the DOACs generally surpassed that of warfarin. In an analysis adjusted for several demographic and clinical confounders, and when compared with patients adherent to a warfarin regimen, those adherent to a DOAC had a 7% lower rate of thromboembolic events, a 36% lower rate of hemorrhagic strokes, an 8% lower rate of any stroke, and a 10% lower rate of bleeds (excluding hemorrhagic strokes), all statistically significant differences, reported Dr. Lakkireddy, medical director of the Kansas City Heart Rhythm Institute in Overland Park, Kan.

The message from this analysis is the importance of maximizing patient adherence, Dr. Lakkireddy said.

Mitchel L. Zoler/MDedge News

“We should not make the false assumption that putting a patient on a DOAC will take care of everything. We need to make it a habit to make sure patients are taking their pills,” he said in an interview. “We were surprised. Our assumption was that the DOACs were more forgiving than warfarin” in poorly compliant patients. “We need to make talking about adherence with patients routine.”

The results also documented that adherence to therapy is better with a DOAC, with a 74% rate of good adherence among the nearly 41,000 patients in the database prescribed a DOAC compared with a 63% rate of good compliance among the more than 42,000 patients prescribed warfarin.

“It’s ironic that we might think low-adherence patients should go on warfarin. That’s sort of backwards,” said Andrew D. Krahn, MD, a cardiac electrophysiologist and professor of medicine at the University of British Columbia in Vancouver. “It’s not biologically plausible” to predict that less adherent patients would do better on warfarin, he noted.

Mitchel L. Zoler/MDedge News

The study run by Dr. Lakkireddy and his associates used data collected by IBM Watson Health Market Scan from about 4 million Medicare patients and 47 million American residents with private insurance during 2012-2016. They focused on the more than 600,000 patients prescribed an anticoagulant during 2014 and 2015, and then narrowed the study group down to just over 83,000 adults with nonvalvular atrial fibrillation, a CHA₂DS₂-VASc score of 2 or more. The patients’ average age was about 74 years.

Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehringer Ingelheim, Bristol Myers Squibb, EstechPharma, Janssen, Pfizer, SentreHeart, and St. Jude. Dr. Krahn has been a consultant to Medtronic and has received research support from Medtronic and Boston Scientific.

[email protected]

SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-03.

 

BOSTON – The direct acting oral anticoagulants boost patient adherence compared with warfarin anticoagulation, but when patients did not adhere to their regimens, those prescribed a new, direct-acting oral anticoagulant had worse outcomes than did patients on warfarin – even patients poorly adherent with warfarin – based on data from more than 80,000 U.S. patients.

Among low-adherence patients, defined as those with adherence rates of 40%-80% based on prescriptions filled, patients with nonvalvular atrial fibrillation and a CHA₂DS₂-VASc score of at least 2 and treated with warfarin had a 3.37/100 patient-years rate of thromboembolic events–driven hospitalizations or emergency department visits, compared with a 4.05/100 patient-years rate among low-adherence patients receiving a direct-acting oral anticoagulant (DOAC), Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. The incidence of strokes of any kind was also lower in the low-adherence warfarin patients compared with the low-adherence DOAC patients, although the relationship flipped for hemorrhagic strokes and bleeds, which were more common in the warfarin patients.

In contrast, when patients were adherent, taking more than 80% of their prescribed drug, the performance of the DOACs generally surpassed that of warfarin. In an analysis adjusted for several demographic and clinical confounders, and when compared with patients adherent to a warfarin regimen, those adherent to a DOAC had a 7% lower rate of thromboembolic events, a 36% lower rate of hemorrhagic strokes, an 8% lower rate of any stroke, and a 10% lower rate of bleeds (excluding hemorrhagic strokes), all statistically significant differences, reported Dr. Lakkireddy, medical director of the Kansas City Heart Rhythm Institute in Overland Park, Kan.

The message from this analysis is the importance of maximizing patient adherence, Dr. Lakkireddy said.

Mitchel L. Zoler/MDedge News

“We should not make the false assumption that putting a patient on a DOAC will take care of everything. We need to make it a habit to make sure patients are taking their pills,” he said in an interview. “We were surprised. Our assumption was that the DOACs were more forgiving than warfarin” in poorly compliant patients. “We need to make talking about adherence with patients routine.”

The results also documented that adherence to therapy is better with a DOAC, with a 74% rate of good adherence among the nearly 41,000 patients in the database prescribed a DOAC compared with a 63% rate of good compliance among the more than 42,000 patients prescribed warfarin.

“It’s ironic that we might think low-adherence patients should go on warfarin. That’s sort of backwards,” said Andrew D. Krahn, MD, a cardiac electrophysiologist and professor of medicine at the University of British Columbia in Vancouver. “It’s not biologically plausible” to predict that less adherent patients would do better on warfarin, he noted.

Mitchel L. Zoler/MDedge News

The study run by Dr. Lakkireddy and his associates used data collected by IBM Watson Health Market Scan from about 4 million Medicare patients and 47 million American residents with private insurance during 2012-2016. They focused on the more than 600,000 patients prescribed an anticoagulant during 2014 and 2015, and then narrowed the study group down to just over 83,000 adults with nonvalvular atrial fibrillation, a CHA₂DS₂-VASc score of 2 or more. The patients’ average age was about 74 years.

Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehringer Ingelheim, Bristol Myers Squibb, EstechPharma, Janssen, Pfizer, SentreHeart, and St. Jude. Dr. Krahn has been a consultant to Medtronic and has received research support from Medtronic and Boston Scientific.

[email protected]

SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-03.

 

WASHINGTON – Tenapanor, a first-in-class agent showed efficacy and safety for treating patients with constipation-predominant irritable bowel syndrome in a phase 3 multicenter, U.S. trial with 593 patients.

These data combined with results from an already reported additional phase 3 trial and a phase 2 study will go to the Food and Drug Administration later in 2018 in an application for marketing approval for tenapanor, William D. Chey, MD, said at the annual Digestive Disease Week.^®

Mitchel L. Zoler/MDedge News

“Tenapanor may represent a novel, effective treatment option” for patients with constipation-predominant irritable bowel syndrome (IBS-C), said Dr. Chey, a professor of medicine and director of the GI Physiology Laboratory at the University of Michigan in Ann Arbor.

The study results met the trial’s primary endpoint, the percentage of patients with a combined response consisting of at least a 30% drop from baseline in reported abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for 6 of the first 12 weeks of treatment. This combined response occurred in 37% of patients treated with tenapanor at a dosage of 50 mg orally b.i.d., compared with a 24% rate among the placebo-control patients, a statistically significant difference, Dr. Chey reported.

The most common adverse effect seen in the tenapanor-treated patients was diarrhea, which occurred in 16% of the drug-treated patients and in 4% of controls. “I think diarrhea is an expected adverse effect,” Dr. Chey said. Overall, treatment-related adverse effects occurred in 23% of tenapanor-treated patients and in 9% of controls, serious adverse effects occurred in 4% of patients on tenapanor and in 3% of controls, and adverse effects leading to treatment discontinuation occurred in 8% on tenapanor and in 1% of controls. Aside from diarrhea, the other most common adverse effects linked with tenapanor treatment were abdominal distension, in 3%, and flatulence, also in 3%.

Tenapanor is an inhibitor of sodium/hydrogen exchanger isoform 3, the predominant intestinal sodium transporter. Through this inhibition tenapanor reduces sodium uptake in the gut, causing increased intestinal fluid volume and shorter transit time and thereby softening stool consistency and increasing bowel movement frequency. Dr. Chey and his colleagues previously reported results from a phase 2 study of tenapanor (Am J Gastroenterol. 2017 Feb;112[2]:763-74), and from a phase 3 study with 606 patients reported at a meeting in late 2017. Results from these two studies were similar to those from the new study.

The current study, A 26-Week Study to Evaluate the Efficacy and Safety of Tenapanor in IBS-C (T3MPO-2) enrolled 593 patients at 114 U.S. centers. Enrolled patients met the Rome III criteria for IBS-C and had an average CSMB frequency of less than 3/week. The researchers treated and followed patients for 26 weeks, although the primary endpoint occurred after 12 weeks on treatment, and 481 of the enrolled patients remained in the study through 26 weeks. At baseline, patients had an average of 0.12 CSBM/week and an average abdominal pain score of 6.26, indicative of moderate to severe abdominal pain. These characteristics identified the enrolled patients as being “on the more severe spectrum of what we see in clinical practice,” Dr. Chey noted.

 

Secondary endpoints included the combined endpoint with the target rate of CSBM achieved in at least 9 of the first 12 weeks, 18% on the active drug and 5% on placebo, and in at least 13 of the 26 weeks on treatment, 36% on tenapanor and 24% on placebo. After 26 weeks on treatment, 55% of patients on tenapanor rated themselves as quite satisfied or very satisfied with their treatment, compared with 33% of the placebo-control patients.

T3MPO-2 was funded by Ardelyx, the company developing tenapanor. Dr. Chey has been a consultant to and has received research funding from Ardelyx and from several other companies. A coauthor on the study was an Ardelyx employee.

[email protected]

On Twitter @mitchelzoler

 

WASHINGTON – Tenapanor, a first-in-class agent showed efficacy and safety for treating patients with constipation-predominant irritable bowel syndrome in a phase 3 multicenter, U.S. trial with 593 patients.

These data combined with results from an already reported additional phase 3 trial and a phase 2 study will go to the Food and Drug Administration later in 2018 in an application for marketing approval for tenapanor, William D. Chey, MD, said at the annual Digestive Disease Week.^®

Mitchel L. Zoler/MDedge News

“Tenapanor may represent a novel, effective treatment option” for patients with constipation-predominant irritable bowel syndrome (IBS-C), said Dr. Chey, a professor of medicine and director of the GI Physiology Laboratory at the University of Michigan in Ann Arbor.

The study results met the trial’s primary endpoint, the percentage of patients with a combined response consisting of at least a 30% drop from baseline in reported abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for 6 of the first 12 weeks of treatment. This combined response occurred in 37% of patients treated with tenapanor at a dosage of 50 mg orally b.i.d., compared with a 24% rate among the placebo-control patients, a statistically significant difference, Dr. Chey reported.

The most common adverse effect seen in the tenapanor-treated patients was diarrhea, which occurred in 16% of the drug-treated patients and in 4% of controls. “I think diarrhea is an expected adverse effect,” Dr. Chey said. Overall, treatment-related adverse effects occurred in 23% of tenapanor-treated patients and in 9% of controls, serious adverse effects occurred in 4% of patients on tenapanor and in 3% of controls, and adverse effects leading to treatment discontinuation occurred in 8% on tenapanor and in 1% of controls. Aside from diarrhea, the other most common adverse effects linked with tenapanor treatment were abdominal distension, in 3%, and flatulence, also in 3%.

Tenapanor is an inhibitor of sodium/hydrogen exchanger isoform 3, the predominant intestinal sodium transporter. Through this inhibition tenapanor reduces sodium uptake in the gut, causing increased intestinal fluid volume and shorter transit time and thereby softening stool consistency and increasing bowel movement frequency. Dr. Chey and his colleagues previously reported results from a phase 2 study of tenapanor (Am J Gastroenterol. 2017 Feb;112[2]:763-74), and from a phase 3 study with 606 patients reported at a meeting in late 2017. Results from these two studies were similar to those from the new study.

The current study, A 26-Week Study to Evaluate the Efficacy and Safety of Tenapanor in IBS-C (T3MPO-2) enrolled 593 patients at 114 U.S. centers. Enrolled patients met the Rome III criteria for IBS-C and had an average CSMB frequency of less than 3/week. The researchers treated and followed patients for 26 weeks, although the primary endpoint occurred after 12 weeks on treatment, and 481 of the enrolled patients remained in the study through 26 weeks. At baseline, patients had an average of 0.12 CSBM/week and an average abdominal pain score of 6.26, indicative of moderate to severe abdominal pain. These characteristics identified the enrolled patients as being “on the more severe spectrum of what we see in clinical practice,” Dr. Chey noted.

 

Secondary endpoints included the combined endpoint with the target rate of CSBM achieved in at least 9 of the first 12 weeks, 18% on the active drug and 5% on placebo, and in at least 13 of the 26 weeks on treatment, 36% on tenapanor and 24% on placebo. After 26 weeks on treatment, 55% of patients on tenapanor rated themselves as quite satisfied or very satisfied with their treatment, compared with 33% of the placebo-control patients.

T3MPO-2 was funded by Ardelyx, the company developing tenapanor. Dr. Chey has been a consultant to and has received research funding from Ardelyx and from several other companies. A coauthor on the study was an Ardelyx employee.

[email protected]

On Twitter @mitchelzoler

 

WASHINGTON – Tenapanor, a first-in-class agent showed efficacy and safety for treating patients with constipation-predominant irritable bowel syndrome in a phase 3 multicenter, U.S. trial with 593 patients.

These data combined with results from an already reported additional phase 3 trial and a phase 2 study will go to the Food and Drug Administration later in 2018 in an application for marketing approval for tenapanor, William D. Chey, MD, said at the annual Digestive Disease Week.^®

Mitchel L. Zoler/MDedge News

“Tenapanor may represent a novel, effective treatment option” for patients with constipation-predominant irritable bowel syndrome (IBS-C), said Dr. Chey, a professor of medicine and director of the GI Physiology Laboratory at the University of Michigan in Ann Arbor.

The study results met the trial’s primary endpoint, the percentage of patients with a combined response consisting of at least a 30% drop from baseline in reported abdominal pain and an increase of at least one complete spontaneous bowel movement (CSBM) per week for 6 of the first 12 weeks of treatment. This combined response occurred in 37% of patients treated with tenapanor at a dosage of 50 mg orally b.i.d., compared with a 24% rate among the placebo-control patients, a statistically significant difference, Dr. Chey reported.

The most common adverse effect seen in the tenapanor-treated patients was diarrhea, which occurred in 16% of the drug-treated patients and in 4% of controls. “I think diarrhea is an expected adverse effect,” Dr. Chey said. Overall, treatment-related adverse effects occurred in 23% of tenapanor-treated patients and in 9% of controls, serious adverse effects occurred in 4% of patients on tenapanor and in 3% of controls, and adverse effects leading to treatment discontinuation occurred in 8% on tenapanor and in 1% of controls. Aside from diarrhea, the other most common adverse effects linked with tenapanor treatment were abdominal distension, in 3%, and flatulence, also in 3%.

Tenapanor is an inhibitor of sodium/hydrogen exchanger isoform 3, the predominant intestinal sodium transporter. Through this inhibition tenapanor reduces sodium uptake in the gut, causing increased intestinal fluid volume and shorter transit time and thereby softening stool consistency and increasing bowel movement frequency. Dr. Chey and his colleagues previously reported results from a phase 2 study of tenapanor (Am J Gastroenterol. 2017 Feb;112[2]:763-74), and from a phase 3 study with 606 patients reported at a meeting in late 2017. Results from these two studies were similar to those from the new study.

The current study, A 26-Week Study to Evaluate the Efficacy and Safety of Tenapanor in IBS-C (T3MPO-2) enrolled 593 patients at 114 U.S. centers. Enrolled patients met the Rome III criteria for IBS-C and had an average CSMB frequency of less than 3/week. The researchers treated and followed patients for 26 weeks, although the primary endpoint occurred after 12 weeks on treatment, and 481 of the enrolled patients remained in the study through 26 weeks. At baseline, patients had an average of 0.12 CSBM/week and an average abdominal pain score of 6.26, indicative of moderate to severe abdominal pain. These characteristics identified the enrolled patients as being “on the more severe spectrum of what we see in clinical practice,” Dr. Chey noted.

 

Secondary endpoints included the combined endpoint with the target rate of CSBM achieved in at least 9 of the first 12 weeks, 18% on the active drug and 5% on placebo, and in at least 13 of the 26 weeks on treatment, 36% on tenapanor and 24% on placebo. After 26 weeks on treatment, 55% of patients on tenapanor rated themselves as quite satisfied or very satisfied with their treatment, compared with 33% of the placebo-control patients.

T3MPO-2 was funded by Ardelyx, the company developing tenapanor. Dr. Chey has been a consultant to and has received research funding from Ardelyx and from several other companies. A coauthor on the study was an Ardelyx employee.

[email protected]

On Twitter @mitchelzoler

 

WASHINGTON – Hospital staffs often fail to treat malnourished, recently admitted patients with supplemental nutrition.

A retrospective review of more than 150,000 patients admitted during a single year at any center within a large, multicenter U.S. hospital system found that even when patients receive oral nutritional supplementation, there is often a substantial delay to its onset.

The data also suggested potential benefits from treating malnutrition with oral nutritional supplementation (ONS). Patients who received ONS had a 10% relative reduction in their rate of 30-day readmission, compared with malnourished patients who did not receive supplements after adjusting for several baseline demographic and clinical variables, Gerard Mullin, MD, said at the annual Digestive Disease Week. His analysis also showed that every doubling of the time from hospital admission to an order for ONS significantly linked with a 6% rise in hospital length of stay.

Mitchel L. Zoler/MDedge News

The findings “highlight the importance of malnutrition screening on admission, starting a nutrition intervention as soon as malnutrition is confirmed, and treating with appropriate ONS,” said Dr. Mullin, a gastroenterologist at Johns Hopkins Medicine in Baltimore and director of the Celiac Disease Clinic. A standard formulation of Ensure was the ONS routinely used at the Johns Hopkins hospitals

“We’re missing malnutrition,” Dr. Mullin said in an interview. The hospital accreditation standards of the Joint Commission call for assessment of the nutritional status of hospitalized patients within 24 hours of admission (Jt Comm J Qual Patient Saf. 2015 Oct;41[10]:469-73). Screening is “not uniformly done,” and when malnutrition is identified, the finding must usually pass through several layers of a hospital’s medico-bureaucratic process before treatment actually starts, he noted. Plus, there’s often dismissal of the importance of intervention. “It’s important to treat patients with ONS sooner than later,” he said.

Dr. Mullin and his associates studied hospital records for 153,161 people admitted to any of the Baltimore-area hospitals in the Johns Hopkins system during October 2016 through the end of September 2017. The hospital staff routinely assessed nutritional status of patients after admission with a two-question screen based on the Malnutrition Screening Tool (Nutrition. 1999 June;15[6]:458-64): Have you had unplanned weight loss of 10 pounds or more during the past 6 months? Have you had decreased oral intake over the past 5 days? This identified 30,284 (20%) who qualified as possibly malnourished by either criterion. The researchers also retrospectively applied a more detailed screen to the patient records using the criteria set by an international consensus guideline committee in 2010 (J Parenter Enteraal Nutr. 2010 Mar-Apr;34[2]:156-9). This identified 8,713 of the hospitalized patients (6%) as malnourished soon after admission. Despite these numbers a scant 274 patients among these 8,713 (3%) actually received ONS, Dr. Mullin reported. In addition, it took an average of 85 hours from the time of each malnourished patient’s admission to when the ONS order appeared in their record.

Dr. Mullin conceded that both the association his group found between treatment with ONS and a reduced rate of 30-day readmission to any of the hospitals in the Johns Hopkins system, and the association between a delay in the time to the start of ONS and length of stay may have been confounded by factors not accounted for in the adjustments they applied. But he maintained that the links are consistent with results from prior studies, and warrant running prospective, randomized studies to better document the impact of ONS on newly admitted patients identified as malnourished.

“We need more of these types of studies and interventional trials to show that ONS makes a difference,” Dr. Mullin said.

The study was sponsored by Abbott, which markets the oral nutritional supplement Ensure. Dr. Mullin had no additional disclosures.

[email protected]

On Twitter @mitchelzoler

SOURCE: Source: Mullin G et al. DDW 2018 presentation 883.

 

WASHINGTON – Hospital staffs often fail to treat malnourished, recently admitted patients with supplemental nutrition.

A retrospective review of more than 150,000 patients admitted during a single year at any center within a large, multicenter U.S. hospital system found that even when patients receive oral nutritional supplementation, there is often a substantial delay to its onset.

The data also suggested potential benefits from treating malnutrition with oral nutritional supplementation (ONS). Patients who received ONS had a 10% relative reduction in their rate of 30-day readmission, compared with malnourished patients who did not receive supplements after adjusting for several baseline demographic and clinical variables, Gerard Mullin, MD, said at the annual Digestive Disease Week. His analysis also showed that every doubling of the time from hospital admission to an order for ONS significantly linked with a 6% rise in hospital length of stay.

Mitchel L. Zoler/MDedge News

The findings “highlight the importance of malnutrition screening on admission, starting a nutrition intervention as soon as malnutrition is confirmed, and treating with appropriate ONS,” said Dr. Mullin, a gastroenterologist at Johns Hopkins Medicine in Baltimore and director of the Celiac Disease Clinic. A standard formulation of Ensure was the ONS routinely used at the Johns Hopkins hospitals

“We’re missing malnutrition,” Dr. Mullin said in an interview. The hospital accreditation standards of the Joint Commission call for assessment of the nutritional status of hospitalized patients within 24 hours of admission (Jt Comm J Qual Patient Saf. 2015 Oct;41[10]:469-73). Screening is “not uniformly done,” and when malnutrition is identified, the finding must usually pass through several layers of a hospital’s medico-bureaucratic process before treatment actually starts, he noted. Plus, there’s often dismissal of the importance of intervention. “It’s important to treat patients with ONS sooner than later,” he said.

Dr. Mullin and his associates studied hospital records for 153,161 people admitted to any of the Baltimore-area hospitals in the Johns Hopkins system during October 2016 through the end of September 2017. The hospital staff routinely assessed nutritional status of patients after admission with a two-question screen based on the Malnutrition Screening Tool (Nutrition. 1999 June;15[6]:458-64): Have you had unplanned weight loss of 10 pounds or more during the past 6 months? Have you had decreased oral intake over the past 5 days? This identified 30,284 (20%) who qualified as possibly malnourished by either criterion. The researchers also retrospectively applied a more detailed screen to the patient records using the criteria set by an international consensus guideline committee in 2010 (J Parenter Enteraal Nutr. 2010 Mar-Apr;34[2]:156-9). This identified 8,713 of the hospitalized patients (6%) as malnourished soon after admission. Despite these numbers a scant 274 patients among these 8,713 (3%) actually received ONS, Dr. Mullin reported. In addition, it took an average of 85 hours from the time of each malnourished patient’s admission to when the ONS order appeared in their record.

Dr. Mullin conceded that both the association his group found between treatment with ONS and a reduced rate of 30-day readmission to any of the hospitals in the Johns Hopkins system, and the association between a delay in the time to the start of ONS and length of stay may have been confounded by factors not accounted for in the adjustments they applied. But he maintained that the links are consistent with results from prior studies, and warrant running prospective, randomized studies to better document the impact of ONS on newly admitted patients identified as malnourished.

“We need more of these types of studies and interventional trials to show that ONS makes a difference,” Dr. Mullin said.

The study was sponsored by Abbott, which markets the oral nutritional supplement Ensure. Dr. Mullin had no additional disclosures.

[email protected]

On Twitter @mitchelzoler

SOURCE: Source: Mullin G et al. DDW 2018 presentation 883.

 

WASHINGTON – Hospital staffs often fail to treat malnourished, recently admitted patients with supplemental nutrition.

A retrospective review of more than 150,000 patients admitted during a single year at any center within a large, multicenter U.S. hospital system found that even when patients receive oral nutritional supplementation, there is often a substantial delay to its onset.

The data also suggested potential benefits from treating malnutrition with oral nutritional supplementation (ONS). Patients who received ONS had a 10% relative reduction in their rate of 30-day readmission, compared with malnourished patients who did not receive supplements after adjusting for several baseline demographic and clinical variables, Gerard Mullin, MD, said at the annual Digestive Disease Week. His analysis also showed that every doubling of the time from hospital admission to an order for ONS significantly linked with a 6% rise in hospital length of stay.

Mitchel L. Zoler/MDedge News

The findings “highlight the importance of malnutrition screening on admission, starting a nutrition intervention as soon as malnutrition is confirmed, and treating with appropriate ONS,” said Dr. Mullin, a gastroenterologist at Johns Hopkins Medicine in Baltimore and director of the Celiac Disease Clinic. A standard formulation of Ensure was the ONS routinely used at the Johns Hopkins hospitals

“We’re missing malnutrition,” Dr. Mullin said in an interview. The hospital accreditation standards of the Joint Commission call for assessment of the nutritional status of hospitalized patients within 24 hours of admission (Jt Comm J Qual Patient Saf. 2015 Oct;41[10]:469-73). Screening is “not uniformly done,” and when malnutrition is identified, the finding must usually pass through several layers of a hospital’s medico-bureaucratic process before treatment actually starts, he noted. Plus, there’s often dismissal of the importance of intervention. “It’s important to treat patients with ONS sooner than later,” he said.

Dr. Mullin and his associates studied hospital records for 153,161 people admitted to any of the Baltimore-area hospitals in the Johns Hopkins system during October 2016 through the end of September 2017. The hospital staff routinely assessed nutritional status of patients after admission with a two-question screen based on the Malnutrition Screening Tool (Nutrition. 1999 June;15[6]:458-64): Have you had unplanned weight loss of 10 pounds or more during the past 6 months? Have you had decreased oral intake over the past 5 days? This identified 30,284 (20%) who qualified as possibly malnourished by either criterion. The researchers also retrospectively applied a more detailed screen to the patient records using the criteria set by an international consensus guideline committee in 2010 (J Parenter Enteraal Nutr. 2010 Mar-Apr;34[2]:156-9). This identified 8,713 of the hospitalized patients (6%) as malnourished soon after admission. Despite these numbers a scant 274 patients among these 8,713 (3%) actually received ONS, Dr. Mullin reported. In addition, it took an average of 85 hours from the time of each malnourished patient’s admission to when the ONS order appeared in their record.

Dr. Mullin conceded that both the association his group found between treatment with ONS and a reduced rate of 30-day readmission to any of the hospitals in the Johns Hopkins system, and the association between a delay in the time to the start of ONS and length of stay may have been confounded by factors not accounted for in the adjustments they applied. But he maintained that the links are consistent with results from prior studies, and warrant running prospective, randomized studies to better document the impact of ONS on newly admitted patients identified as malnourished.

“We need more of these types of studies and interventional trials to show that ONS makes a difference,” Dr. Mullin said.

The study was sponsored by Abbott, which markets the oral nutritional supplement Ensure. Dr. Mullin had no additional disclosures.

[email protected]

On Twitter @mitchelzoler

SOURCE: Source: Mullin G et al. DDW 2018 presentation 883.

 

WASHINGTON – Hospitalizations for shingles is twice as common among patients with inflammatory bowel disease than in the general U.S. population, based on analysis of data from the National Inpatient Sample.

Mitchel L. Zoler/MDedge News

This elevated risk for patients with inflammatory bowel disease (IBD) to develop a herpes zoster virus (HZV) reactivation severe enough to put them in the hospital makes it especially important for IBD patients to receive immunization against shingles, especially now that a more effective vaccine is available, Daniela G. Vinsard, MD, said at the annual Digestive Disease Week^®. Ideally, IBD patients should receive the full course of the adjuvanted, recombinant zoster vaccine Shingrix before starting an immunosuppressive regimen, said Dr. Vinsard, a physician at the University of Connecticut, Farmington.

This finding, which underscored the susceptibility of IBD patients to shingles because of their immunosuppressive treatments and the importance of vaccination, recently became even more relevant when the Food and Drug Administration approved tofacitinib (Xeljanz) to treat ulcerative colitis in late May, commented Gil Y. Melmed, MD, director of clinical inflammatory bowel disease at Cedars-Sinai Medical Center, Los Angeles. Tofacitinib, which may be an attractive option to some patients as an oral immunomodulator, carries a black box warning about the added risk for certain serious infections while taking the drug, including HZV. Recent recommendations from the American College of Gastroenterology said that IBD patients aged 51 years or older should “strongly consider” HZV vaccination, including immunosuppressed patients (Am J Gastroenterol. 2017 Feb; 112[2]:241-58). The introduction of a potentially popular drug for ulcerative colitis that’s known to pose a risk for shingles might lead to a stronger recommendation for vaccination in the near future, Dr. Melmed said in an interview.

The study Dr. Vinsard reported used data collected by the National Inpatient Sample from 2012 to September 2015, which represented, with weighting, more than 142 million hospitalized American patients. From this data set she and her associates identified 7,180 IBD patients hospitalized with a primary diagnosis of a vaccine-preventable disease, and about 589,000 weighted patients hospitalized for a vaccine-preventable disease but without IBD. The selection also focused on patients aged 18-65 years. Dr. Vinsard said that she excluded older patients to eliminate advanced age as a cause of immunosuppression.

Among the IBD patients, HZV was the most frequent primary diagnosis, causing 35% of these hospitalizations. Other common infectious causes of hospitalization in this group were hepatitis B virus in 31% of cases, influenza in 22%, pneumonia in 9%, and other types of infections in the remaining 3%. In contrast, hepatitis B caused 35% of hospitalizations in patients without IBD, influenza caused 29%, pneumonia caused 14%, HZV caused 19%, and other infections accounted for 3% of admissions.

In a multivariate analysis that controlled for diabetes, HIV infection, cancer, and transplantation, the IBD patients had more than twice the rate of hospitalization for shingles, compared with the patients without IBD, Dr. Vinsard said. When broken down by specific disease type, the rate of HZV infection was 110% higher among ulcerative colitis patients, compared with the general population, and was 140% higher in Crohn’s disease patients, both statistically significant differences.

An additional finding from the analysis was that during the 4 years of study, the rate of hospitalizations of IBD patients for influenza steadily rose, from about 10% in 2012 to nearly 30% in 2015.

Dr. Vinsard reported no disclosures. Dr. Melmed reported consulting with Pfizer, the company that markets tofacitinib, and with several other companies that market biological agents.

[email protected]

 

WASHINGTON – Hospitalizations for shingles is twice as common among patients with inflammatory bowel disease than in the general U.S. population, based on analysis of data from the National Inpatient Sample.

Mitchel L. Zoler/MDedge News

This elevated risk for patients with inflammatory bowel disease (IBD) to develop a herpes zoster virus (HZV) reactivation severe enough to put them in the hospital makes it especially important for IBD patients to receive immunization against shingles, especially now that a more effective vaccine is available, Daniela G. Vinsard, MD, said at the annual Digestive Disease Week^®. Ideally, IBD patients should receive the full course of the adjuvanted, recombinant zoster vaccine Shingrix before starting an immunosuppressive regimen, said Dr. Vinsard, a physician at the University of Connecticut, Farmington.

This finding, which underscored the susceptibility of IBD patients to shingles because of their immunosuppressive treatments and the importance of vaccination, recently became even more relevant when the Food and Drug Administration approved tofacitinib (Xeljanz) to treat ulcerative colitis in late May, commented Gil Y. Melmed, MD, director of clinical inflammatory bowel disease at Cedars-Sinai Medical Center, Los Angeles. Tofacitinib, which may be an attractive option to some patients as an oral immunomodulator, carries a black box warning about the added risk for certain serious infections while taking the drug, including HZV. Recent recommendations from the American College of Gastroenterology said that IBD patients aged 51 years or older should “strongly consider” HZV vaccination, including immunosuppressed patients (Am J Gastroenterol. 2017 Feb; 112[2]:241-58). The introduction of a potentially popular drug for ulcerative colitis that’s known to pose a risk for shingles might lead to a stronger recommendation for vaccination in the near future, Dr. Melmed said in an interview.

The study Dr. Vinsard reported used data collected by the National Inpatient Sample from 2012 to September 2015, which represented, with weighting, more than 142 million hospitalized American patients. From this data set she and her associates identified 7,180 IBD patients hospitalized with a primary diagnosis of a vaccine-preventable disease, and about 589,000 weighted patients hospitalized for a vaccine-preventable disease but without IBD. The selection also focused on patients aged 18-65 years. Dr. Vinsard said that she excluded older patients to eliminate advanced age as a cause of immunosuppression.

Among the IBD patients, HZV was the most frequent primary diagnosis, causing 35% of these hospitalizations. Other common infectious causes of hospitalization in this group were hepatitis B virus in 31% of cases, influenza in 22%, pneumonia in 9%, and other types of infections in the remaining 3%. In contrast, hepatitis B caused 35% of hospitalizations in patients without IBD, influenza caused 29%, pneumonia caused 14%, HZV caused 19%, and other infections accounted for 3% of admissions.

In a multivariate analysis that controlled for diabetes, HIV infection, cancer, and transplantation, the IBD patients had more than twice the rate of hospitalization for shingles, compared with the patients without IBD, Dr. Vinsard said. When broken down by specific disease type, the rate of HZV infection was 110% higher among ulcerative colitis patients, compared with the general population, and was 140% higher in Crohn’s disease patients, both statistically significant differences.

An additional finding from the analysis was that during the 4 years of study, the rate of hospitalizations of IBD patients for influenza steadily rose, from about 10% in 2012 to nearly 30% in 2015.

Dr. Vinsard reported no disclosures. Dr. Melmed reported consulting with Pfizer, the company that markets tofacitinib, and with several other companies that market biological agents.

[email protected]

 

WASHINGTON – Hospitalizations for shingles is twice as common among patients with inflammatory bowel disease than in the general U.S. population, based on analysis of data from the National Inpatient Sample.

Mitchel L. Zoler/MDedge News

This elevated risk for patients with inflammatory bowel disease (IBD) to develop a herpes zoster virus (HZV) reactivation severe enough to put them in the hospital makes it especially important for IBD patients to receive immunization against shingles, especially now that a more effective vaccine is available, Daniela G. Vinsard, MD, said at the annual Digestive Disease Week^®. Ideally, IBD patients should receive the full course of the adjuvanted, recombinant zoster vaccine Shingrix before starting an immunosuppressive regimen, said Dr. Vinsard, a physician at the University of Connecticut, Farmington.

This finding, which underscored the susceptibility of IBD patients to shingles because of their immunosuppressive treatments and the importance of vaccination, recently became even more relevant when the Food and Drug Administration approved tofacitinib (Xeljanz) to treat ulcerative colitis in late May, commented Gil Y. Melmed, MD, director of clinical inflammatory bowel disease at Cedars-Sinai Medical Center, Los Angeles. Tofacitinib, which may be an attractive option to some patients as an oral immunomodulator, carries a black box warning about the added risk for certain serious infections while taking the drug, including HZV. Recent recommendations from the American College of Gastroenterology said that IBD patients aged 51 years or older should “strongly consider” HZV vaccination, including immunosuppressed patients (Am J Gastroenterol. 2017 Feb; 112[2]:241-58). The introduction of a potentially popular drug for ulcerative colitis that’s known to pose a risk for shingles might lead to a stronger recommendation for vaccination in the near future, Dr. Melmed said in an interview.

The study Dr. Vinsard reported used data collected by the National Inpatient Sample from 2012 to September 2015, which represented, with weighting, more than 142 million hospitalized American patients. From this data set she and her associates identified 7,180 IBD patients hospitalized with a primary diagnosis of a vaccine-preventable disease, and about 589,000 weighted patients hospitalized for a vaccine-preventable disease but without IBD. The selection also focused on patients aged 18-65 years. Dr. Vinsard said that she excluded older patients to eliminate advanced age as a cause of immunosuppression.

Among the IBD patients, HZV was the most frequent primary diagnosis, causing 35% of these hospitalizations. Other common infectious causes of hospitalization in this group were hepatitis B virus in 31% of cases, influenza in 22%, pneumonia in 9%, and other types of infections in the remaining 3%. In contrast, hepatitis B caused 35% of hospitalizations in patients without IBD, influenza caused 29%, pneumonia caused 14%, HZV caused 19%, and other infections accounted for 3% of admissions.

In a multivariate analysis that controlled for diabetes, HIV infection, cancer, and transplantation, the IBD patients had more than twice the rate of hospitalization for shingles, compared with the patients without IBD, Dr. Vinsard said. When broken down by specific disease type, the rate of HZV infection was 110% higher among ulcerative colitis patients, compared with the general population, and was 140% higher in Crohn’s disease patients, both statistically significant differences.

An additional finding from the analysis was that during the 4 years of study, the rate of hospitalizations of IBD patients for influenza steadily rose, from about 10% in 2012 to nearly 30% in 2015.

Dr. Vinsard reported no disclosures. Dr. Melmed reported consulting with Pfizer, the company that markets tofacitinib, and with several other companies that market biological agents.

[email protected]

 

BOSTON – New ways for implanted cardiac rhythm devices to work without need for transvenous leads are in clinical testing, reflecting a keen interest in getting leads out of the vascular space and potentially cutting risks for infections, pneumothorax, hematoma, and the possible need for future lead extraction.

Leads are “the Achilles heel” of pacemakers and defibrillators; “there are too many places where the wire can break,” John D. Day, MD, said in an interview during the annual scientific sessions of the Heart Rhythm Society. Eliminating transvenous leads, or any type of lead for that matter, “solves a lot of problems” that currently occur with implanted cardiac devices, said Dr. Day, a cardiac electrophysiologist with Intermountain Health in Murray, Utah.

Researchers presented results from initial clinical studies with two different alternatives to conventional device leads at the meeting.

The Acute Extravascular Defibrillation, Pacing, and Electrogram (ASD2) study tested a substernal lead in 79 patients enrolled at multiple centers in the United States and elsewhere. The lead’s design uses a minimally invasive subxiphoid approach with substernal lead advancement using a blunt tunneling rod, explained Lucas V.A. Boersma, MD, a professor of cardiology at the Academic Medical Center University in Amsterdam. Placed between the sternum and heart, the lead sits just beside the ventricles to provide both ventricular pacing and defibrillation, unlike existing subcutaneously placed leads that do not allow pacing and require high energy for defibrillation. It took a median of 12 minutes to place the lead, Dr. Boersma said.

Testing demonstrated successful ventricular pacing capture in 76 of 78 patients (97%) who underwent this testing, he reported. A single 30-joule shock delivered via the substernal lead resulted in successful defibrillation of induced fibrillation in 102 of 123 fibrillation events (83%). Six patients had seven adverse events that resolved without sequelae for all but two events. The two events with greater clinical impact included one patient with asystolic cardiac arrest 36 hours after lead placement who developed decompensated heart failure and required medical management, and one patient with pericardial effusion and tamponade who required supportive care.

Mitchel L. Zoler/MDedge News

The results showed the feasibility of a substernal lead, Dr. Boersma concluded. “There is a learning curve” for placing the lead, he noted. “The subdural space where you place the lead is empty, but you have to be careful to stay within the subdural space,” in a procedure that relies on fluoroscopic guidance.

“We are very used to working in the transvenous space” for lead placement, “and leaving that space is outside the comfort zone” for many clinicians, Dr. Boersma noted. “It will take time to adopt these new technologies, and obviously we need more proof” of efficacy and safety.

 

The second study examined a novel approach that modified the control algorithm of the Micra leadless single-chamber pacing device, approved for U.S. marketing in 2016, so that it used information collected by a built-in accelerometer to detect atrial contractions and produce atrial-ventricular (AV) synchrony in patients with AV block.

The MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study enrolled 70 patients at 12 centers worldwide and collected evaluable data from 64 patients. The average time spent in AV synchrony using this AV pacing was 87% in all patients, with an 80% average rate of AV synchrony in the 33 enrolled patients who had high-degree block, said Larry A. Chinitz, MD, professor of medicine and director of the Heart Rhythm Center at New York University Langone Health. Concurrently with his report at the meeting, the results also appeared in an article online (Heart Rhythm. 2018 May 11. doi: 10.1016/j.hrthm.2018.05.004).

Mitchel L. Zoler/MDedge News

“Complications were extraordinarily minimal,” he also reported. “The results suggest we can offer leadless pacing to a much larger group of patients,” those who need dual-chamber pacing, Dr. Chinitz said.

The current leadless pacemaker is very limited as a single-chamber pacing device because it can only help patients who have permanent atrial fibrillation and a slow ventricular response and hence only need single-chamber pacing, about 14% of all patients who need cardiac pacing, said Dr. Chinitz. Using the accelerometer information appears to make the Micra device suitable for the much larger number of patients who have AV block. “You effectively have dual-chamber pacing but with a single pellet. This is a simple and attractive way to do it,” Dr. Day commented. “You get a two-for-one” that potentially could triple the number of patients who could benefit from the Micra leadless device, he estimated.

 

[email protected]

On Twitter @mitchelzoler

SOURCE: Boersma L et al. Heart Rhythm 2018, Abstract B-LBCT03-03; Chinitz L et al. Heart Rhythm 2018, Abstract B-LBCT03-04.

 

BOSTON – New ways for implanted cardiac rhythm devices to work without need for transvenous leads are in clinical testing, reflecting a keen interest in getting leads out of the vascular space and potentially cutting risks for infections, pneumothorax, hematoma, and the possible need for future lead extraction.

Leads are “the Achilles heel” of pacemakers and defibrillators; “there are too many places where the wire can break,” John D. Day, MD, said in an interview during the annual scientific sessions of the Heart Rhythm Society. Eliminating transvenous leads, or any type of lead for that matter, “solves a lot of problems” that currently occur with implanted cardiac devices, said Dr. Day, a cardiac electrophysiologist with Intermountain Health in Murray, Utah.

Researchers presented results from initial clinical studies with two different alternatives to conventional device leads at the meeting.

The Acute Extravascular Defibrillation, Pacing, and Electrogram (ASD2) study tested a substernal lead in 79 patients enrolled at multiple centers in the United States and elsewhere. The lead’s design uses a minimally invasive subxiphoid approach with substernal lead advancement using a blunt tunneling rod, explained Lucas V.A. Boersma, MD, a professor of cardiology at the Academic Medical Center University in Amsterdam. Placed between the sternum and heart, the lead sits just beside the ventricles to provide both ventricular pacing and defibrillation, unlike existing subcutaneously placed leads that do not allow pacing and require high energy for defibrillation. It took a median of 12 minutes to place the lead, Dr. Boersma said.

Testing demonstrated successful ventricular pacing capture in 76 of 78 patients (97%) who underwent this testing, he reported. A single 30-joule shock delivered via the substernal lead resulted in successful defibrillation of induced fibrillation in 102 of 123 fibrillation events (83%). Six patients had seven adverse events that resolved without sequelae for all but two events. The two events with greater clinical impact included one patient with asystolic cardiac arrest 36 hours after lead placement who developed decompensated heart failure and required medical management, and one patient with pericardial effusion and tamponade who required supportive care.

Mitchel L. Zoler/MDedge News

The results showed the feasibility of a substernal lead, Dr. Boersma concluded. “There is a learning curve” for placing the lead, he noted. “The subdural space where you place the lead is empty, but you have to be careful to stay within the subdural space,” in a procedure that relies on fluoroscopic guidance.

“We are very used to working in the transvenous space” for lead placement, “and leaving that space is outside the comfort zone” for many clinicians, Dr. Boersma noted. “It will take time to adopt these new technologies, and obviously we need more proof” of efficacy and safety.

 

The second study examined a novel approach that modified the control algorithm of the Micra leadless single-chamber pacing device, approved for U.S. marketing in 2016, so that it used information collected by a built-in accelerometer to detect atrial contractions and produce atrial-ventricular (AV) synchrony in patients with AV block.

The MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study enrolled 70 patients at 12 centers worldwide and collected evaluable data from 64 patients. The average time spent in AV synchrony using this AV pacing was 87% in all patients, with an 80% average rate of AV synchrony in the 33 enrolled patients who had high-degree block, said Larry A. Chinitz, MD, professor of medicine and director of the Heart Rhythm Center at New York University Langone Health. Concurrently with his report at the meeting, the results also appeared in an article online (Heart Rhythm. 2018 May 11. doi: 10.1016/j.hrthm.2018.05.004).

Mitchel L. Zoler/MDedge News

“Complications were extraordinarily minimal,” he also reported. “The results suggest we can offer leadless pacing to a much larger group of patients,” those who need dual-chamber pacing, Dr. Chinitz said.

The current leadless pacemaker is very limited as a single-chamber pacing device because it can only help patients who have permanent atrial fibrillation and a slow ventricular response and hence only need single-chamber pacing, about 14% of all patients who need cardiac pacing, said Dr. Chinitz. Using the accelerometer information appears to make the Micra device suitable for the much larger number of patients who have AV block. “You effectively have dual-chamber pacing but with a single pellet. This is a simple and attractive way to do it,” Dr. Day commented. “You get a two-for-one” that potentially could triple the number of patients who could benefit from the Micra leadless device, he estimated.

 

[email protected]

On Twitter @mitchelzoler

SOURCE: Boersma L et al. Heart Rhythm 2018, Abstract B-LBCT03-03; Chinitz L et al. Heart Rhythm 2018, Abstract B-LBCT03-04.

 

BOSTON – New ways for implanted cardiac rhythm devices to work without need for transvenous leads are in clinical testing, reflecting a keen interest in getting leads out of the vascular space and potentially cutting risks for infections, pneumothorax, hematoma, and the possible need for future lead extraction.

Leads are “the Achilles heel” of pacemakers and defibrillators; “there are too many places where the wire can break,” John D. Day, MD, said in an interview during the annual scientific sessions of the Heart Rhythm Society. Eliminating transvenous leads, or any type of lead for that matter, “solves a lot of problems” that currently occur with implanted cardiac devices, said Dr. Day, a cardiac electrophysiologist with Intermountain Health in Murray, Utah.

Researchers presented results from initial clinical studies with two different alternatives to conventional device leads at the meeting.

The Acute Extravascular Defibrillation, Pacing, and Electrogram (ASD2) study tested a substernal lead in 79 patients enrolled at multiple centers in the United States and elsewhere. The lead’s design uses a minimally invasive subxiphoid approach with substernal lead advancement using a blunt tunneling rod, explained Lucas V.A. Boersma, MD, a professor of cardiology at the Academic Medical Center University in Amsterdam. Placed between the sternum and heart, the lead sits just beside the ventricles to provide both ventricular pacing and defibrillation, unlike existing subcutaneously placed leads that do not allow pacing and require high energy for defibrillation. It took a median of 12 minutes to place the lead, Dr. Boersma said.

Testing demonstrated successful ventricular pacing capture in 76 of 78 patients (97%) who underwent this testing, he reported. A single 30-joule shock delivered via the substernal lead resulted in successful defibrillation of induced fibrillation in 102 of 123 fibrillation events (83%). Six patients had seven adverse events that resolved without sequelae for all but two events. The two events with greater clinical impact included one patient with asystolic cardiac arrest 36 hours after lead placement who developed decompensated heart failure and required medical management, and one patient with pericardial effusion and tamponade who required supportive care.

Mitchel L. Zoler/MDedge News

The results showed the feasibility of a substernal lead, Dr. Boersma concluded. “There is a learning curve” for placing the lead, he noted. “The subdural space where you place the lead is empty, but you have to be careful to stay within the subdural space,” in a procedure that relies on fluoroscopic guidance.

“We are very used to working in the transvenous space” for lead placement, “and leaving that space is outside the comfort zone” for many clinicians, Dr. Boersma noted. “It will take time to adopt these new technologies, and obviously we need more proof” of efficacy and safety.

 

The second study examined a novel approach that modified the control algorithm of the Micra leadless single-chamber pacing device, approved for U.S. marketing in 2016, so that it used information collected by a built-in accelerometer to detect atrial contractions and produce atrial-ventricular (AV) synchrony in patients with AV block.

The MARVEL (Micra Atrial Tracking Using a Ventricular Accelerometer) study enrolled 70 patients at 12 centers worldwide and collected evaluable data from 64 patients. The average time spent in AV synchrony using this AV pacing was 87% in all patients, with an 80% average rate of AV synchrony in the 33 enrolled patients who had high-degree block, said Larry A. Chinitz, MD, professor of medicine and director of the Heart Rhythm Center at New York University Langone Health. Concurrently with his report at the meeting, the results also appeared in an article online (Heart Rhythm. 2018 May 11. doi: 10.1016/j.hrthm.2018.05.004).

Mitchel L. Zoler/MDedge News

“Complications were extraordinarily minimal,” he also reported. “The results suggest we can offer leadless pacing to a much larger group of patients,” those who need dual-chamber pacing, Dr. Chinitz said.

The current leadless pacemaker is very limited as a single-chamber pacing device because it can only help patients who have permanent atrial fibrillation and a slow ventricular response and hence only need single-chamber pacing, about 14% of all patients who need cardiac pacing, said Dr. Chinitz. Using the accelerometer information appears to make the Micra device suitable for the much larger number of patients who have AV block. “You effectively have dual-chamber pacing but with a single pellet. This is a simple and attractive way to do it,” Dr. Day commented. “You get a two-for-one” that potentially could triple the number of patients who could benefit from the Micra leadless device, he estimated.

 

[email protected]

On Twitter @mitchelzoler

SOURCE: Boersma L et al. Heart Rhythm 2018, Abstract B-LBCT03-03; Chinitz L et al. Heart Rhythm 2018, Abstract B-LBCT03-04.

 

BOSTON – About half of patients who present with a new onset of frequent premature ventricular contractions without obvious underlying heart disease had an underlying myocardial inflammation that was often responsive to immunosuppressive treatment, according to a single-center series of 107 patients.

“Early diagnosis and appropriate treatment with immunosuppressive therapy can significantly affect the clinical course,” although large-scale, multicenter, randomized trials must confirm this as an effective management approach, Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. He stressed that the anecdotal efficacy seen in this series with immunosuppressive therapy and selected use of ablation treatment for the premature ventricular contractions (PVCs) applies only to patients with new-onset PVCs that occur at a rate of at least 5,000 during 24 hours who also have myocardial inflammation identified by a PET scan showing increased fluorodeoxyglucose (FDG) uptake.

Mitchel L. Zoler/MDedge News

Of the 46 patients who underwent this treatment, 31 (67%) had an optimal response – resolution of FDG uptake by the myocardium and at least an 80% cut in PVC count – and another 7 patients (15%) responded but less robustly during an average follow-up of 6 months. In contrast, six of the nine untreated patients either progressed or had no change in their disease severity, while three untreated patients showed suboptimal improvement, reported Dr. Lakkireddy, medical director of the Kansas City Heart Rhythm Institute in Overland Park, Kan.

The apparent impact of immunosuppressive treatment was “profound,” Dr. Lakkireddy said. The treatment usually involved prednisone and, in many patients, a second immunosuppressant agent such as azathioprine, cyclophosphamide, or methotrexate. The results suggest “a unique opportunity to intervene early with immunosuppression to change the natural course of the disease. PVCs may be the earliest sign of a disease process” featuring myocardial inflammation.

The data came from the Myocarditis and Ventricular Arrhythmia (MAVERIC) registry that Dr. Lakkireddy and his associates started because “we began seeing patients referred for ablations without underlying heart disease who had suddenly presented with a lot of PVCs,” he recalled, an observation that led them to systematically study these patients in an “arduous” process that involved several tests. One hundred seven patients met the registry’s inclusion criteria for new onset of frequent PVCs without apparent underlying heart disease, and roughly half of these patients showed clear evidence of myocardial inflammation by FDG and PET imaging. “If the PET is negative, I don’t worry about myocarditis, “ Dr. Lakkireddy said.

The 55 patients with apparent myocarditis on PET imaging, out of the 107 patients examined generally, had lower left ventricular (LV) ejection fractions averaging 46%, compared with 51% among the patients without myocarditis The patients with myocarditis further subdivided into 27 with preserved LV function, with an average ejection fraction of 60%, and 28 with a reduced LV function, with an average ejection fraction of 40%. The researchers saw an optimal response to immunosuppressive therapy in 18 of the 23 patients (78%) with preserved ejection fractions who received this treatment and in 13 of the 24 patients (54%) with diminished LV ejection fractions who got immunosuppressive therapy.

Twenty-eight of the 55 patients with myocarditis on PET imaging underwent a right-sided biopsy during their work-up, and 13 of these 28 biopsies (46%) showed a lymphocytic infiltrate of a type often seen in patients with postviral myocarditis. Seven of the 28 biopsied patients (25%) had completely normal-appearing cardiac tissue.

Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehinger Ingelheim, Bristol-Myers Squibb, Estech, Janssen, Pfizer, SentreHeart, and St. Jude.

[email protected]

SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-02.
 

 

BOSTON – About half of patients who present with a new onset of frequent premature ventricular contractions without obvious underlying heart disease had an underlying myocardial inflammation that was often responsive to immunosuppressive treatment, according to a single-center series of 107 patients.

“Early diagnosis and appropriate treatment with immunosuppressive therapy can significantly affect the clinical course,” although large-scale, multicenter, randomized trials must confirm this as an effective management approach, Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. He stressed that the anecdotal efficacy seen in this series with immunosuppressive therapy and selected use of ablation treatment for the premature ventricular contractions (PVCs) applies only to patients with new-onset PVCs that occur at a rate of at least 5,000 during 24 hours who also have myocardial inflammation identified by a PET scan showing increased fluorodeoxyglucose (FDG) uptake.

Mitchel L. Zoler/MDedge News

Of the 46 patients who underwent this treatment, 31 (67%) had an optimal response – resolution of FDG uptake by the myocardium and at least an 80% cut in PVC count – and another 7 patients (15%) responded but less robustly during an average follow-up of 6 months. In contrast, six of the nine untreated patients either progressed or had no change in their disease severity, while three untreated patients showed suboptimal improvement, reported Dr. Lakkireddy, medical director of the Kansas City Heart Rhythm Institute in Overland Park, Kan.

The apparent impact of immunosuppressive treatment was “profound,” Dr. Lakkireddy said. The treatment usually involved prednisone and, in many patients, a second immunosuppressant agent such as azathioprine, cyclophosphamide, or methotrexate. The results suggest “a unique opportunity to intervene early with immunosuppression to change the natural course of the disease. PVCs may be the earliest sign of a disease process” featuring myocardial inflammation.

The data came from the Myocarditis and Ventricular Arrhythmia (MAVERIC) registry that Dr. Lakkireddy and his associates started because “we began seeing patients referred for ablations without underlying heart disease who had suddenly presented with a lot of PVCs,” he recalled, an observation that led them to systematically study these patients in an “arduous” process that involved several tests. One hundred seven patients met the registry’s inclusion criteria for new onset of frequent PVCs without apparent underlying heart disease, and roughly half of these patients showed clear evidence of myocardial inflammation by FDG and PET imaging. “If the PET is negative, I don’t worry about myocarditis, “ Dr. Lakkireddy said.

The 55 patients with apparent myocarditis on PET imaging, out of the 107 patients examined generally, had lower left ventricular (LV) ejection fractions averaging 46%, compared with 51% among the patients without myocarditis The patients with myocarditis further subdivided into 27 with preserved LV function, with an average ejection fraction of 60%, and 28 with a reduced LV function, with an average ejection fraction of 40%. The researchers saw an optimal response to immunosuppressive therapy in 18 of the 23 patients (78%) with preserved ejection fractions who received this treatment and in 13 of the 24 patients (54%) with diminished LV ejection fractions who got immunosuppressive therapy.

Twenty-eight of the 55 patients with myocarditis on PET imaging underwent a right-sided biopsy during their work-up, and 13 of these 28 biopsies (46%) showed a lymphocytic infiltrate of a type often seen in patients with postviral myocarditis. Seven of the 28 biopsied patients (25%) had completely normal-appearing cardiac tissue.

Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehinger Ingelheim, Bristol-Myers Squibb, Estech, Janssen, Pfizer, SentreHeart, and St. Jude.

[email protected]

SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-02.
 

 

BOSTON – About half of patients who present with a new onset of frequent premature ventricular contractions without obvious underlying heart disease had an underlying myocardial inflammation that was often responsive to immunosuppressive treatment, according to a single-center series of 107 patients.

“Early diagnosis and appropriate treatment with immunosuppressive therapy can significantly affect the clinical course,” although large-scale, multicenter, randomized trials must confirm this as an effective management approach, Dhanunjaya Lakkireddy, MD, said at the annual scientific sessions of the Heart Rhythm Society. He stressed that the anecdotal efficacy seen in this series with immunosuppressive therapy and selected use of ablation treatment for the premature ventricular contractions (PVCs) applies only to patients with new-onset PVCs that occur at a rate of at least 5,000 during 24 hours who also have myocardial inflammation identified by a PET scan showing increased fluorodeoxyglucose (FDG) uptake.

Mitchel L. Zoler/MDedge News

Of the 46 patients who underwent this treatment, 31 (67%) had an optimal response – resolution of FDG uptake by the myocardium and at least an 80% cut in PVC count – and another 7 patients (15%) responded but less robustly during an average follow-up of 6 months. In contrast, six of the nine untreated patients either progressed or had no change in their disease severity, while three untreated patients showed suboptimal improvement, reported Dr. Lakkireddy, medical director of the Kansas City Heart Rhythm Institute in Overland Park, Kan.

The apparent impact of immunosuppressive treatment was “profound,” Dr. Lakkireddy said. The treatment usually involved prednisone and, in many patients, a second immunosuppressant agent such as azathioprine, cyclophosphamide, or methotrexate. The results suggest “a unique opportunity to intervene early with immunosuppression to change the natural course of the disease. PVCs may be the earliest sign of a disease process” featuring myocardial inflammation.

The data came from the Myocarditis and Ventricular Arrhythmia (MAVERIC) registry that Dr. Lakkireddy and his associates started because “we began seeing patients referred for ablations without underlying heart disease who had suddenly presented with a lot of PVCs,” he recalled, an observation that led them to systematically study these patients in an “arduous” process that involved several tests. One hundred seven patients met the registry’s inclusion criteria for new onset of frequent PVCs without apparent underlying heart disease, and roughly half of these patients showed clear evidence of myocardial inflammation by FDG and PET imaging. “If the PET is negative, I don’t worry about myocarditis, “ Dr. Lakkireddy said.

The 55 patients with apparent myocarditis on PET imaging, out of the 107 patients examined generally, had lower left ventricular (LV) ejection fractions averaging 46%, compared with 51% among the patients without myocarditis The patients with myocarditis further subdivided into 27 with preserved LV function, with an average ejection fraction of 60%, and 28 with a reduced LV function, with an average ejection fraction of 40%. The researchers saw an optimal response to immunosuppressive therapy in 18 of the 23 patients (78%) with preserved ejection fractions who received this treatment and in 13 of the 24 patients (54%) with diminished LV ejection fractions who got immunosuppressive therapy.

Twenty-eight of the 55 patients with myocarditis on PET imaging underwent a right-sided biopsy during their work-up, and 13 of these 28 biopsies (46%) showed a lymphocytic infiltrate of a type often seen in patients with postviral myocarditis. Seven of the 28 biopsied patients (25%) had completely normal-appearing cardiac tissue.

Dr. Lakkireddy has been a consultant to or has received research support from Biosense Webster, Boehinger Ingelheim, Bristol-Myers Squibb, Estech, Janssen, Pfizer, SentreHeart, and St. Jude.

[email protected]

SOURCE: Lakkireddy D et al. Heart Rhythm 2018, Abstract B-LBCT02-02.
 

 

BOSTON – A single set of four injections with botulinum toxin into neuron-containing cardiac fat pads of patients during open-chest cardiac artery bypass surgery led to a long-term cut in the cumulative incidence of atrial tachyarrhythmias during 3-year follow-up in a pilot, sham-controlled study with 60 patients at two Russian centers.

“Because the favorable reduction of atrial fibrillation [AF] outlasted the anticipated botulinum toxin effects on autonomic nervous system activity, this may represent a form of autonomic reverse remodeling” triggered by just one injection of the paralyzing toxin at each of four intracardiac fat pads, Alexander B. Romanov, MD, said at the annual scientific sessions of the Heart Rhythm Society. Botulinum toxin (BT) blocks neuronal release of acetylcholine, thereby interfering with cholinergic neurotransmission and producing hypothesized neurologic remodeling, explained Dr. Romanov, a researcher at the Meshalkin National Medical Research Center in Novosibirsk, Russia.

The current report of 3-year follow-up follows similarly encouraging results seen after 30 days (J Am Coll Cardiol. 2014 Aug;64[6]:628-9) and 12 months (Circ Arrhythm Electrophysiol. 2015 Dec;8[6]:1334-41) in the same group of 60 patients randomized to receive either the BT injections at four intracardiac fat pads or sham injections during standard coronary artery bypass grafting. The researchers enrolled patients at high risk for atrial tachyarrhythmias based on a history of paroxysmal AF. After 36 months, the primary endpoint of incident atrial tachyarrhythmia occurred in 50% of the 30 sham-control patients and in 23% of those treated with BT, a 64% relative risk reduction in a proportional hazard model that was statistically significant (P = .02). The Kaplan-Meier plot of the primary endpoint over time in each of the two subgroups suggested continued separation of the curves during the third year of follow-up.

The 3-year results also showed statistically significant differences or trends favoring BT injections for several other clinical outcomes. Two deaths and two strokes occurred, all among the control patients. Two patients required a total of three hospitalizations during follow-up in the BT-treated group, compared with 10 patients hospitalized a total of 21 times in the control arm. Clinicians prescribed antiarrhythmic drugs to six of the BT-treated patients and to 15 of the controls.

All patients received an implanted heart rhythm monitor during their bypass surgery, and the researchers measured AF burden – the percentage of time during which AF occurred. After 12 months, 24 months, and 36 months, the AF burden averaged 0.2%, 1.6%, and 1.2%, respectively, in the BT-treated patients and 1.9%, 9.5%, and 6.9% in the sham-control patients.

Mitchel L. Zoler/MDedge News

Based on these promising findings Allergen, a company that markets a BT formulation (Botox) plans to start later in 2018 a randomized trial with about 300 patients to further test the efficacy of BT injections for preventing AF, Dr. Romanov said. He and his associates are also exploring the feasibility and efficacy of injecting BT into cardiac sites via a percutaneous needle to preclude the need for open surgery.

“We don’t know why this works, but it’s a fascinating new approach that is worthy of further study,” commented Kalyanam Shivkumar, MD, professor and director of the Cardiac Arrhythmia Center at the University of California, Los Angeles, and designated discussant for the report.

“This is an extremely exciting study, but it remains inconclusive because how it works is not fully understood,” commented Andrew D. Krahn, MD, professor and chief of cardiology at the University of British Columbia in Vancouver.

[email protected]

 

BOSTON – A single set of four injections with botulinum toxin into neuron-containing cardiac fat pads of patients during open-chest cardiac artery bypass surgery led to a long-term cut in the cumulative incidence of atrial tachyarrhythmias during 3-year follow-up in a pilot, sham-controlled study with 60 patients at two Russian centers.

“Because the favorable reduction of atrial fibrillation [AF] outlasted the anticipated botulinum toxin effects on autonomic nervous system activity, this may represent a form of autonomic reverse remodeling” triggered by just one injection of the paralyzing toxin at each of four intracardiac fat pads, Alexander B. Romanov, MD, said at the annual scientific sessions of the Heart Rhythm Society. Botulinum toxin (BT) blocks neuronal release of acetylcholine, thereby interfering with cholinergic neurotransmission and producing hypothesized neurologic remodeling, explained Dr. Romanov, a researcher at the Meshalkin National Medical Research Center in Novosibirsk, Russia.

The current report of 3-year follow-up follows similarly encouraging results seen after 30 days (J Am Coll Cardiol. 2014 Aug;64[6]:628-9) and 12 months (Circ Arrhythm Electrophysiol. 2015 Dec;8[6]:1334-41) in the same group of 60 patients randomized to receive either the BT injections at four intracardiac fat pads or sham injections during standard coronary artery bypass grafting. The researchers enrolled patients at high risk for atrial tachyarrhythmias based on a history of paroxysmal AF. After 36 months, the primary endpoint of incident atrial tachyarrhythmia occurred in 50% of the 30 sham-control patients and in 23% of those treated with BT, a 64% relative risk reduction in a proportional hazard model that was statistically significant (P = .02). The Kaplan-Meier plot of the primary endpoint over time in each of the two subgroups suggested continued separation of the curves during the third year of follow-up.

The 3-year results also showed statistically significant differences or trends favoring BT injections for several other clinical outcomes. Two deaths and two strokes occurred, all among the control patients. Two patients required a total of three hospitalizations during follow-up in the BT-treated group, compared with 10 patients hospitalized a total of 21 times in the control arm. Clinicians prescribed antiarrhythmic drugs to six of the BT-treated patients and to 15 of the controls.

All patients received an implanted heart rhythm monitor during their bypass surgery, and the researchers measured AF burden – the percentage of time during which AF occurred. After 12 months, 24 months, and 36 months, the AF burden averaged 0.2%, 1.6%, and 1.2%, respectively, in the BT-treated patients and 1.9%, 9.5%, and 6.9% in the sham-control patients.

Mitchel L. Zoler/MDedge News

Based on these promising findings Allergen, a company that markets a BT formulation (Botox) plans to start later in 2018 a randomized trial with about 300 patients to further test the efficacy of BT injections for preventing AF, Dr. Romanov said. He and his associates are also exploring the feasibility and efficacy of injecting BT into cardiac sites via a percutaneous needle to preclude the need for open surgery.

“We don’t know why this works, but it’s a fascinating new approach that is worthy of further study,” commented Kalyanam Shivkumar, MD, professor and director of the Cardiac Arrhythmia Center at the University of California, Los Angeles, and designated discussant for the report.

“This is an extremely exciting study, but it remains inconclusive because how it works is not fully understood,” commented Andrew D. Krahn, MD, professor and chief of cardiology at the University of British Columbia in Vancouver.

[email protected]

 

BOSTON – A single set of four injections with botulinum toxin into neuron-containing cardiac fat pads of patients during open-chest cardiac artery bypass surgery led to a long-term cut in the cumulative incidence of atrial tachyarrhythmias during 3-year follow-up in a pilot, sham-controlled study with 60 patients at two Russian centers.

“Because the favorable reduction of atrial fibrillation [AF] outlasted the anticipated botulinum toxin effects on autonomic nervous system activity, this may represent a form of autonomic reverse remodeling” triggered by just one injection of the paralyzing toxin at each of four intracardiac fat pads, Alexander B. Romanov, MD, said at the annual scientific sessions of the Heart Rhythm Society. Botulinum toxin (BT) blocks neuronal release of acetylcholine, thereby interfering with cholinergic neurotransmission and producing hypothesized neurologic remodeling, explained Dr. Romanov, a researcher at the Meshalkin National Medical Research Center in Novosibirsk, Russia.

The current report of 3-year follow-up follows similarly encouraging results seen after 30 days (J Am Coll Cardiol. 2014 Aug;64[6]:628-9) and 12 months (Circ Arrhythm Electrophysiol. 2015 Dec;8[6]:1334-41) in the same group of 60 patients randomized to receive either the BT injections at four intracardiac fat pads or sham injections during standard coronary artery bypass grafting. The researchers enrolled patients at high risk for atrial tachyarrhythmias based on a history of paroxysmal AF. After 36 months, the primary endpoint of incident atrial tachyarrhythmia occurred in 50% of the 30 sham-control patients and in 23% of those treated with BT, a 64% relative risk reduction in a proportional hazard model that was statistically significant (P = .02). The Kaplan-Meier plot of the primary endpoint over time in each of the two subgroups suggested continued separation of the curves during the third year of follow-up.

The 3-year results also showed statistically significant differences or trends favoring BT injections for several other clinical outcomes. Two deaths and two strokes occurred, all among the control patients. Two patients required a total of three hospitalizations during follow-up in the BT-treated group, compared with 10 patients hospitalized a total of 21 times in the control arm. Clinicians prescribed antiarrhythmic drugs to six of the BT-treated patients and to 15 of the controls.

All patients received an implanted heart rhythm monitor during their bypass surgery, and the researchers measured AF burden – the percentage of time during which AF occurred. After 12 months, 24 months, and 36 months, the AF burden averaged 0.2%, 1.6%, and 1.2%, respectively, in the BT-treated patients and 1.9%, 9.5%, and 6.9% in the sham-control patients.

Mitchel L. Zoler/MDedge News

Based on these promising findings Allergen, a company that markets a BT formulation (Botox) plans to start later in 2018 a randomized trial with about 300 patients to further test the efficacy of BT injections for preventing AF, Dr. Romanov said. He and his associates are also exploring the feasibility and efficacy of injecting BT into cardiac sites via a percutaneous needle to preclude the need for open surgery.

“We don’t know why this works, but it’s a fascinating new approach that is worthy of further study,” commented Kalyanam Shivkumar, MD, professor and director of the Cardiac Arrhythmia Center at the University of California, Los Angeles, and designated discussant for the report.

“This is an extremely exciting study, but it remains inconclusive because how it works is not fully understood,” commented Andrew D. Krahn, MD, professor and chief of cardiology at the University of British Columbia in Vancouver.

[email protected]