BOSTON – When given with ribavirin, a fixed-dose combination of sofosbuvir/velpatasvir (Epclusa) achieved a sustained viral response at 12 weeks (SVR-12) in 94% of decompensated cirrhotic patients with hepatitis C virus (HCV) genotypes 1-6 infection, according to Zobair M. Younossi, MD.

Patients with and without cirrhosis also reported meaningful improvements across a variety of outcome measures after successfully completing treatment with Epclusa or sofosbuvir (Harvoni), said Dr. Younossi of Inova Fairfax Hospital in Falls Church, Va. “Although on-treatment patient-reported outcomes improved more with ribavirin-free regimens, post-SVR improvements were similar,” regardless of whether patients had received ribavirin, he reported at the annual meeting of the American Association for the Study of Liver Diseases.

BOSTON – When given with ribavirin, a fixed-dose combination of sofosbuvir/velpatasvir (Epclusa) achieved a sustained viral response at 12 weeks (SVR-12) in 94% of decompensated cirrhotic patients with hepatitis C virus (HCV) genotypes 1-6 infection, according to Zobair M. Younossi, MD.

Patients with and without cirrhosis also reported meaningful improvements across a variety of outcome measures after successfully completing treatment with Epclusa or sofosbuvir (Harvoni), said Dr. Younossi of Inova Fairfax Hospital in Falls Church, Va. “Although on-treatment patient-reported outcomes improved more with ribavirin-free regimens, post-SVR improvements were similar,” regardless of whether patients had received ribavirin, he reported at the annual meeting of the American Association for the Study of Liver Diseases.

BOSTON – When given with ribavirin, a fixed-dose combination of sofosbuvir/velpatasvir (Epclusa) achieved a sustained viral response at 12 weeks (SVR-12) in 94% of decompensated cirrhotic patients with hepatitis C virus (HCV) genotypes 1-6 infection, according to Zobair M. Younossi, MD.

Patients with and without cirrhosis also reported meaningful improvements across a variety of outcome measures after successfully completing treatment with Epclusa or sofosbuvir (Harvoni), said Dr. Younossi of Inova Fairfax Hospital in Falls Church, Va. “Although on-treatment patient-reported outcomes improved more with ribavirin-free regimens, post-SVR improvements were similar,” regardless of whether patients had received ribavirin, he reported at the annual meeting of the American Association for the Study of Liver Diseases.

Primary chest-wall leiomyosarcoma (LMS) is an uncommon, malignant, soft-tissue tumor that most often affects the extremities. Malignant LMS originates from mesenchymal cells with smooth muscle differentiation. It is rare in adults, forming only 7% of all soft-tissue sarcomas (STS), but it is the most common STS. In adults, this type of tumor is usually found in the retroperitoneum and extremities.¹ Chest-wall LMS is rare and most often occurs in men aged 50-70 years.² When LMS is associated with rib destruction, it may mimic a primary bone tumor or metastasis. We present here the case of histologically proven chest-wall sarcoma with associated rib destruction that was initially mistaken on imaging for either a metastasis or primary bone tumor.

Case presentation and summary
A 69-year-old man presented to the emergency department complaining of pain over the right side of the chest. The pain, which was pleuritic in nature, had worsened over the previous 6 months and was severe at presentation. The patient had no fever, shortness of breath, or loss of weight. He had no history of chest trauma or chest wall radiation, and nothing noteworthy was discovered in his medical history. Subsequent test results for hemoglobin, white blood cell count, lymphocyte count, and cardiac enzymes were normal.

A frontal chest radiograph showed an osteolytic destructive lesion involving the posterior right 6th rib (Figure 1). A contrast-enhanced computedtomography (CE-CT) scan of the chest showed a heterogeneously enhancing, ovoid, soft-tissue mass of 5.6 x 3.6 cm (2.2 x 1.2 in) centered on the postero- lateral right 6th rib, with associated rib erosion. There was another 2.0-cm (0.8-in) subpleural nodule in the left upper lobe (Figure 2).

Click on the PDF icon below to read the full article.
 

Primary chest-wall leiomyosarcoma (LMS) is an uncommon, malignant, soft-tissue tumor that most often affects the extremities. Malignant LMS originates from mesenchymal cells with smooth muscle differentiation. It is rare in adults, forming only 7% of all soft-tissue sarcomas (STS), but it is the most common STS. In adults, this type of tumor is usually found in the retroperitoneum and extremities.¹ Chest-wall LMS is rare and most often occurs in men aged 50-70 years.² When LMS is associated with rib destruction, it may mimic a primary bone tumor or metastasis. We present here the case of histologically proven chest-wall sarcoma with associated rib destruction that was initially mistaken on imaging for either a metastasis or primary bone tumor.

Case presentation and summary
A 69-year-old man presented to the emergency department complaining of pain over the right side of the chest. The pain, which was pleuritic in nature, had worsened over the previous 6 months and was severe at presentation. The patient had no fever, shortness of breath, or loss of weight. He had no history of chest trauma or chest wall radiation, and nothing noteworthy was discovered in his medical history. Subsequent test results for hemoglobin, white blood cell count, lymphocyte count, and cardiac enzymes were normal.

A frontal chest radiograph showed an osteolytic destructive lesion involving the posterior right 6th rib (Figure 1). A contrast-enhanced computedtomography (CE-CT) scan of the chest showed a heterogeneously enhancing, ovoid, soft-tissue mass of 5.6 x 3.6 cm (2.2 x 1.2 in) centered on the postero- lateral right 6th rib, with associated rib erosion. There was another 2.0-cm (0.8-in) subpleural nodule in the left upper lobe (Figure 2).

Click on the PDF icon below to read the full article.
 

Primary chest-wall leiomyosarcoma (LMS) is an uncommon, malignant, soft-tissue tumor that most often affects the extremities. Malignant LMS originates from mesenchymal cells with smooth muscle differentiation. It is rare in adults, forming only 7% of all soft-tissue sarcomas (STS), but it is the most common STS. In adults, this type of tumor is usually found in the retroperitoneum and extremities.¹ Chest-wall LMS is rare and most often occurs in men aged 50-70 years.² When LMS is associated with rib destruction, it may mimic a primary bone tumor or metastasis. We present here the case of histologically proven chest-wall sarcoma with associated rib destruction that was initially mistaken on imaging for either a metastasis or primary bone tumor.

Case presentation and summary
A 69-year-old man presented to the emergency department complaining of pain over the right side of the chest. The pain, which was pleuritic in nature, had worsened over the previous 6 months and was severe at presentation. The patient had no fever, shortness of breath, or loss of weight. He had no history of chest trauma or chest wall radiation, and nothing noteworthy was discovered in his medical history. Subsequent test results for hemoglobin, white blood cell count, lymphocyte count, and cardiac enzymes were normal.

A frontal chest radiograph showed an osteolytic destructive lesion involving the posterior right 6th rib (Figure 1). A contrast-enhanced computedtomography (CE-CT) scan of the chest showed a heterogeneously enhancing, ovoid, soft-tissue mass of 5.6 x 3.6 cm (2.2 x 1.2 in) centered on the postero- lateral right 6th rib, with associated rib erosion. There was another 2.0-cm (0.8-in) subpleural nodule in the left upper lobe (Figure 2).

Click on the PDF icon below to read the full article.
 

WASHINGTON – Putting patients on urate-lowering therapy after their first flare of gout and treating urate levels to target appeared to reduce risk for additional disease flares over a 2-year period, based on results from 314 patients in a randomized, double-blind, placebo-controlled trial.

Among patients with early gout – those experiencing their first gout flare or a second flare that occurred more than 1 year after their first flare – the risk for one or more gout flares during the course of the study was 41% in the placebo group and 29% in the group of patients given febuxostat, a statistically significant difference (P = .033).

The significant advantage for active therapy to prevent flares was seen at 6-12 months, 12-18 months, and 18-24 months.

Alice Goodman/Frontline Medical News

WASHINGTON – Putting patients on urate-lowering therapy after their first flare of gout and treating urate levels to target appeared to reduce risk for additional disease flares over a 2-year period, based on results from 314 patients in a randomized, double-blind, placebo-controlled trial.

Among patients with early gout – those experiencing their first gout flare or a second flare that occurred more than 1 year after their first flare – the risk for one or more gout flares during the course of the study was 41% in the placebo group and 29% in the group of patients given febuxostat, a statistically significant difference (P = .033).

The significant advantage for active therapy to prevent flares was seen at 6-12 months, 12-18 months, and 18-24 months.

Alice Goodman/Frontline Medical News

WASHINGTON – Putting patients on urate-lowering therapy after their first flare of gout and treating urate levels to target appeared to reduce risk for additional disease flares over a 2-year period, based on results from 314 patients in a randomized, double-blind, placebo-controlled trial.

Among patients with early gout – those experiencing their first gout flare or a second flare that occurred more than 1 year after their first flare – the risk for one or more gout flares during the course of the study was 41% in the placebo group and 29% in the group of patients given febuxostat, a statistically significant difference (P = .033).

The significant advantage for active therapy to prevent flares was seen at 6-12 months, 12-18 months, and 18-24 months.

Alice Goodman/Frontline Medical News

BOSTON – All phenotypes of nonalcoholic fatty liver disease (NAFLD) can progress or regress even without pharmacologic intervention, according to a prospective longitudinal study of 394 patients.

Weight loss and baseline NAFLD Activity Score predicted resolution of NAFLD, while weight gain and rising serum transaminases predicted progression to nonalcoholic steatohepatitis (NASH), Arun J. Sanyal, MD, said at the annual meeting of the American Association for the Study of Liver Diseases. Baseline and subsequent NAFLD Activity Score also was “a strong predictor of fibrosis progression or regression,” as was AST, portal inflammation, and baseline fibrosis stage, said Dr. Sanyal of Virginia Commonwealth University in Richmond, Va.

NAFLD comprises two main phenotypes, fatty liver and steatohepatitis. “The phenotype can change over time, and both phenotypes can be associated with fibrosis,” Dr. Sanyal noted. To better understand trends and clinical correlates for these phenotypes, he and his associates analyzed prospectively collected clinical and biopsy data from the NASH Clinical Research Network of the National Institutes of Diabetes and Digestive and Kidney Diseases. Each patient attended multiple clinic visits and underwent two liver biopsies at least 1 year and usually 4-5 years apart, which were interpreted by a masked central pathology review committee.

At baseline, 75 patients had fatty liver without steatohepatitis, of which only 13% resolved and 44% progressed to borderline or definite steatohepatitis. Similarly, among 74 patients with borderline steatohepatitis at baseline, only 22% regressed to fatty liver disease without steatohepatitis, while 43% progressed to definite steatohepatitis. The remaining 245 patients had definite steatohepatitis at baseline, of which 58% failed to regress at all, 20% regressed to borderline, 11% regressed to fatty liver disease without steatohepatitis, and 11% regressed to normal.

The investigators also performed a multivariable analysis of 197 patients with complete data. After the investigators controlled for serum insulin level, alkaline phosphatase level, NAS, and the presence of metabolic syndrome, each 10-U/L increase in ALT more than doubled the odds of progression from fatty liver without steatohepatitis to NASH (odds ratio, 2.2; 95% confidence interval, 1.1 to 4.1; P = .02). The association was even stronger for AST (OR, 3.5; 95% CI, 1.2 to 10.4; P = .03), and each 1-kg gain in body weight increased the odds of progression to NASH by 70% (OR, 1.7; 95% CI, 1.1 to 2.5; P = .01). In contrast, resolution of NAFLD was associated with weight loss (OR per 1 kg, 0.9; P less than .001) and lower baseline NAFLD Activity Score (OR, 0.7; P = .04).

About one in four patients had evidence of fibrosis at baseline, and 44% had at least stage 1 fibrosis at follow-up biopsy. Patients whose NAFLD progressed to a more severe phenotype were much more likely to have evidence of progressive fibrosis than were those whose NAFLD did not progress (OR, 7.2; 95% CI, 2.1 to 21.5; P less than .001), and there was no evidence that time between liver biopsies influenced this relationship. Among patients with definite NASH who had stage 0 fibrosis at baseline, 50% progressed to at least 1 fibrosis stage over the next 6.8 years, and 50% progressed to at least 2 stages over 9.6 years. Patients whose baseline NAFLD Activity Scores were between 1 and 4 were most likely to experience regression of fibrosis, while those with scores between 5 and 8 were more likely to have worsening fibrosis. Patients with severe baseline NAFLD Activity Score component scores for steatosis, lobular inflammation, and ballooning also were significantly more likely to have progressive fibrosis than were those with baseline NAFLD Activity Scores of 0 or 1. Furthermore, increasing NAFLD Activity Score over time predicted fibrosis progression.

Diabetes did not seem to affect fibrosis progression or regression, Dr. Sanyal noted. However, baseline portal inflammation predicted worsening fibrosis (P less than .01), as did baseline and subsequent elevations in AST (P less than .001), insulin (P = .03), and NAS (P less than 001), and baseline ballooning (P less than .01).

The investigators reported that the study had no sponsors. Dr. Sanyal disclosed ties to a wide number of drug companies.
 

BOSTON – All phenotypes of nonalcoholic fatty liver disease (NAFLD) can progress or regress even without pharmacologic intervention, according to a prospective longitudinal study of 394 patients.

Weight loss and baseline NAFLD Activity Score predicted resolution of NAFLD, while weight gain and rising serum transaminases predicted progression to nonalcoholic steatohepatitis (NASH), Arun J. Sanyal, MD, said at the annual meeting of the American Association for the Study of Liver Diseases. Baseline and subsequent NAFLD Activity Score also was “a strong predictor of fibrosis progression or regression,” as was AST, portal inflammation, and baseline fibrosis stage, said Dr. Sanyal of Virginia Commonwealth University in Richmond, Va.

NAFLD comprises two main phenotypes, fatty liver and steatohepatitis. “The phenotype can change over time, and both phenotypes can be associated with fibrosis,” Dr. Sanyal noted. To better understand trends and clinical correlates for these phenotypes, he and his associates analyzed prospectively collected clinical and biopsy data from the NASH Clinical Research Network of the National Institutes of Diabetes and Digestive and Kidney Diseases. Each patient attended multiple clinic visits and underwent two liver biopsies at least 1 year and usually 4-5 years apart, which were interpreted by a masked central pathology review committee.

At baseline, 75 patients had fatty liver without steatohepatitis, of which only 13% resolved and 44% progressed to borderline or definite steatohepatitis. Similarly, among 74 patients with borderline steatohepatitis at baseline, only 22% regressed to fatty liver disease without steatohepatitis, while 43% progressed to definite steatohepatitis. The remaining 245 patients had definite steatohepatitis at baseline, of which 58% failed to regress at all, 20% regressed to borderline, 11% regressed to fatty liver disease without steatohepatitis, and 11% regressed to normal.

The investigators also performed a multivariable analysis of 197 patients with complete data. After the investigators controlled for serum insulin level, alkaline phosphatase level, NAS, and the presence of metabolic syndrome, each 10-U/L increase in ALT more than doubled the odds of progression from fatty liver without steatohepatitis to NASH (odds ratio, 2.2; 95% confidence interval, 1.1 to 4.1; P = .02). The association was even stronger for AST (OR, 3.5; 95% CI, 1.2 to 10.4; P = .03), and each 1-kg gain in body weight increased the odds of progression to NASH by 70% (OR, 1.7; 95% CI, 1.1 to 2.5; P = .01). In contrast, resolution of NAFLD was associated with weight loss (OR per 1 kg, 0.9; P less than .001) and lower baseline NAFLD Activity Score (OR, 0.7; P = .04).

About one in four patients had evidence of fibrosis at baseline, and 44% had at least stage 1 fibrosis at follow-up biopsy. Patients whose NAFLD progressed to a more severe phenotype were much more likely to have evidence of progressive fibrosis than were those whose NAFLD did not progress (OR, 7.2; 95% CI, 2.1 to 21.5; P less than .001), and there was no evidence that time between liver biopsies influenced this relationship. Among patients with definite NASH who had stage 0 fibrosis at baseline, 50% progressed to at least 1 fibrosis stage over the next 6.8 years, and 50% progressed to at least 2 stages over 9.6 years. Patients whose baseline NAFLD Activity Scores were between 1 and 4 were most likely to experience regression of fibrosis, while those with scores between 5 and 8 were more likely to have worsening fibrosis. Patients with severe baseline NAFLD Activity Score component scores for steatosis, lobular inflammation, and ballooning also were significantly more likely to have progressive fibrosis than were those with baseline NAFLD Activity Scores of 0 or 1. Furthermore, increasing NAFLD Activity Score over time predicted fibrosis progression.

Diabetes did not seem to affect fibrosis progression or regression, Dr. Sanyal noted. However, baseline portal inflammation predicted worsening fibrosis (P less than .01), as did baseline and subsequent elevations in AST (P less than .001), insulin (P = .03), and NAS (P less than 001), and baseline ballooning (P less than .01).

The investigators reported that the study had no sponsors. Dr. Sanyal disclosed ties to a wide number of drug companies.
 

BOSTON – All phenotypes of nonalcoholic fatty liver disease (NAFLD) can progress or regress even without pharmacologic intervention, according to a prospective longitudinal study of 394 patients.

Weight loss and baseline NAFLD Activity Score predicted resolution of NAFLD, while weight gain and rising serum transaminases predicted progression to nonalcoholic steatohepatitis (NASH), Arun J. Sanyal, MD, said at the annual meeting of the American Association for the Study of Liver Diseases. Baseline and subsequent NAFLD Activity Score also was “a strong predictor of fibrosis progression or regression,” as was AST, portal inflammation, and baseline fibrosis stage, said Dr. Sanyal of Virginia Commonwealth University in Richmond, Va.

NAFLD comprises two main phenotypes, fatty liver and steatohepatitis. “The phenotype can change over time, and both phenotypes can be associated with fibrosis,” Dr. Sanyal noted. To better understand trends and clinical correlates for these phenotypes, he and his associates analyzed prospectively collected clinical and biopsy data from the NASH Clinical Research Network of the National Institutes of Diabetes and Digestive and Kidney Diseases. Each patient attended multiple clinic visits and underwent two liver biopsies at least 1 year and usually 4-5 years apart, which were interpreted by a masked central pathology review committee.

At baseline, 75 patients had fatty liver without steatohepatitis, of which only 13% resolved and 44% progressed to borderline or definite steatohepatitis. Similarly, among 74 patients with borderline steatohepatitis at baseline, only 22% regressed to fatty liver disease without steatohepatitis, while 43% progressed to definite steatohepatitis. The remaining 245 patients had definite steatohepatitis at baseline, of which 58% failed to regress at all, 20% regressed to borderline, 11% regressed to fatty liver disease without steatohepatitis, and 11% regressed to normal.

The investigators also performed a multivariable analysis of 197 patients with complete data. After the investigators controlled for serum insulin level, alkaline phosphatase level, NAS, and the presence of metabolic syndrome, each 10-U/L increase in ALT more than doubled the odds of progression from fatty liver without steatohepatitis to NASH (odds ratio, 2.2; 95% confidence interval, 1.1 to 4.1; P = .02). The association was even stronger for AST (OR, 3.5; 95% CI, 1.2 to 10.4; P = .03), and each 1-kg gain in body weight increased the odds of progression to NASH by 70% (OR, 1.7; 95% CI, 1.1 to 2.5; P = .01). In contrast, resolution of NAFLD was associated with weight loss (OR per 1 kg, 0.9; P less than .001) and lower baseline NAFLD Activity Score (OR, 0.7; P = .04).

About one in four patients had evidence of fibrosis at baseline, and 44% had at least stage 1 fibrosis at follow-up biopsy. Patients whose NAFLD progressed to a more severe phenotype were much more likely to have evidence of progressive fibrosis than were those whose NAFLD did not progress (OR, 7.2; 95% CI, 2.1 to 21.5; P less than .001), and there was no evidence that time between liver biopsies influenced this relationship. Among patients with definite NASH who had stage 0 fibrosis at baseline, 50% progressed to at least 1 fibrosis stage over the next 6.8 years, and 50% progressed to at least 2 stages over 9.6 years. Patients whose baseline NAFLD Activity Scores were between 1 and 4 were most likely to experience regression of fibrosis, while those with scores between 5 and 8 were more likely to have worsening fibrosis. Patients with severe baseline NAFLD Activity Score component scores for steatosis, lobular inflammation, and ballooning also were significantly more likely to have progressive fibrosis than were those with baseline NAFLD Activity Scores of 0 or 1. Furthermore, increasing NAFLD Activity Score over time predicted fibrosis progression.

Diabetes did not seem to affect fibrosis progression or regression, Dr. Sanyal noted. However, baseline portal inflammation predicted worsening fibrosis (P less than .01), as did baseline and subsequent elevations in AST (P less than .001), insulin (P = .03), and NAS (P less than 001), and baseline ballooning (P less than .01).

The investigators reported that the study had no sponsors. Dr. Sanyal disclosed ties to a wide number of drug companies.
 

Multiple myeloma accounts for about 1% of all cancers and for 10% of hematologic malignancies in the United States. This report describes the cases of 2 patients with multiple myeloma who developed CNS involvement after autologous stem cell transplant in the context of extramedullary disease.

Click on the PDF icon at the top of this introduction to read the full article.

Multiple myeloma accounts for about 1% of all cancers and for 10% of hematologic malignancies in the United States. This report describes the cases of 2 patients with multiple myeloma who developed CNS involvement after autologous stem cell transplant in the context of extramedullary disease.

Click on the PDF icon at the top of this introduction to read the full article.

Multiple myeloma accounts for about 1% of all cancers and for 10% of hematologic malignancies in the United States. This report describes the cases of 2 patients with multiple myeloma who developed CNS involvement after autologous stem cell transplant in the context of extramedullary disease.

Click on the PDF icon at the top of this introduction to read the full article.

LAS VEGAS—At the American Academy of Neurology’s Fall 2016 Conference, Robert M. Pascuzzi, MD, presented several case videos to illustrate recent advances in caring for patients with rare neuromuscular disorders, including myasthenia gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis (ALS). Dr. Pascuzzi is Chair of the Department of Neurology at Indiana University School of Medicine in Indianapolis.

Myasthenia Gravis

The first case, a 55-year-old woman with a six-month history of double vision and swallowing trouble, also expressed the Cogan lid twitch, which is “pathognomonic for myasthenia gravis,” Dr. Pascuzzi said.

“It’s nice to have a test to confirm your clinical suspicions,” he said, noting that antibodies to the acetylcholine receptor (AChR) yield “almost perfect specificity” for myasthenia gravis. Other antibodies in use or under study to confirm this diagnosis include muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), agrin, and cortactin.

The recently completed International Thymectomy Trial, which followed 126 patients for three years, found that those randomly assigned to transsternal thymectomy plus prednisone versus prednisone alone had significantly improved clinical outcomes, as measured on the Quantitative Myasthenia Gravis scale. Patients also required less prednisone, 44 mg versus 60 mg (alternate days), and fewer patients in the thymectomy group required azathioprine (17% versus 48%) or were hospitalized for exacerbations (9% versus 37%).

“Up until this study, nobody was completely sure this treatment worked,” Dr. Pascuzzi said.

Lambert-Eaton Syndrome

In the second case, a woman presented with a six-month history of falling down after her legs gave out on her. She also complained of dry mouth and, on examination, had proximal weakness and no muscle stretch reflexes.

Serology and EMG testing confirmed Lambert-Eaton myasthenic syndrome, a paraneoplastic syndrome. Half the patients with this syndrome have small cell carcinoma, Dr. Pascuzzi said, usually lung, due to smoking. In 64% of cases, the SOX1 antibody is positive.

Treatment approaches include treating the cancer; and 3,4 diaminopyridine, pyridostigmine, and immunotherapy.

Duchenne Muscular Dystrophy

A six-year-old boy with progressive clumsiness was found to have Duchenne muscular dystrophy, a diagnosis with “huge” genetic implications for his three younger brothers, Dr. Pascuzzi said. By age 20, patients are usually on ventilators.

Recently, the FDA granted accelerated approval to the first drug to treat Duchenne muscular dystrophy—Exondys 51 (eteplirsen). The drug “is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13% of the population with Duchenne muscular dystrophy,” the FDA noted.

However, eteplirsen is not without controversy, Dr. Pascuzzi said. “There’s no documented clinical benefit. If you show there is a little more dystrophin being deposited and built in muscle, what does that mean? As of today, nobody knows. So that is an issue I think the FDA Advisory Panel and other people are worried about. And then, at $300,000 a year, it is not a financially insignificant impact.”

As the drug is used, further studies and data “will eventually show that it does or does not have clinical benefit,” Dr. Pascuzzi said. Patients must undergo testing for the mutation. Reported adverse events include balance issues and vomiting.

Amyotrophic Lateral Sclerosis

The third and fourth cases focused on a 53-year-old man with 12 months of progressive decline in speech and swallowing, and a woman with similar symptoms who also would laugh for no apparent reason. Both cases were displaying the pseudobulbar affect of ALS.

About 5% to 10% of all ALS cases are familial and, in 40% to 50%, the most common gene is C9orf72. Less common is the SOD1 gene (20%), with those carrying its A4V mutation generally dying within one year. Other mutations include TDP-43 (5%), and FUS (5%).

Dr. Pascuzzi cautioned that cognitive impairment among patients with ALS can be as high as 40% and cannot usually be detected on a bedside exam. Up to 15% of patients “get a frank, overt, clinically significant dementia, usually a frontotemporal syndrome.”

Treatment approaches include use of multidisciplinary clinics, ankle-foot orthosis, tools for activities of daily living, bilevel positive airway pressure, chin tuck, and power chairs; drugs include riluzole, dextromethorphan/quinidine for pseudobulbar affect, and drugs for spasticity.

He said it is important to address fear, depression, and anxiety in patients with ALS, and not to overlook the caregiver: “We are slowly but surely melting down our caregivers.”

A recent study in Lancet Neurology helped Dr. Pascuzzi and colleagues decide against diaphragm pacing for patients with respiratory insufficiency due to ALS, due to the potential for harm. “I would be cautious about pursuing this,” he said.

Despite the many failed controlled trials over the past 20 years, much investigational work is being done on ALS therapeutics, from injection of antisense molecules to tirasemtiv to stem cells, immune therapy, neuro-protection, and high fat/calorie diet, “so there is reason to be hopeful.”

Stem cell transplantation, in particular, is something he said his patients always ask him about. Two forms, “both important,” have undergone fairly extensive clinical investigation.

In the first, spinal cord-derived neural stem cells are transplanted into the spinal cord.

“The people that drive this work are convinced this is not stem cells that turn into motor neurons and replace lost or failing motor neurons, but instead these are stem cells that provide an environment that is more favorable for sick motor neurons,” Dr. Pascuzzi said. “They secrete nerve growth factors and transport proteins to improve the environment.”

The second approach, autologous stem cell treatment, is a “culture-based method for inducing mesenchymal stem cells to secrete neurotrophic factors,” he said, which has been “shown to be protective in several animal models of neurodegenerative diseases.”

—Debra Hughes

Suggested Reading

DiPALS Writing Committee on behalf of the DiPALS Study Group Collaborators. Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2015;14(9);883-892.

Glass JD, Hertzberg VS, Boulis NM, et al. Transplantation of spinal cord-derived neural stem cells for ALS: analysis of phase 1 and 2 trials. Neurology. 2016;87(4):392-400.

Petrou P, Gothelf Y, Argov Z, et al. Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials. JAMA Neurol. 2016;73(3):337-344.

U.S. Food and Drug Administration. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. FDA News Release. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm. Accessed November 4, 2016.

Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375(6):511-522.

LAS VEGAS—At the American Academy of Neurology’s Fall 2016 Conference, Robert M. Pascuzzi, MD, presented several case videos to illustrate recent advances in caring for patients with rare neuromuscular disorders, including myasthenia gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis (ALS). Dr. Pascuzzi is Chair of the Department of Neurology at Indiana University School of Medicine in Indianapolis.

Myasthenia Gravis

The first case, a 55-year-old woman with a six-month history of double vision and swallowing trouble, also expressed the Cogan lid twitch, which is “pathognomonic for myasthenia gravis,” Dr. Pascuzzi said.

“It’s nice to have a test to confirm your clinical suspicions,” he said, noting that antibodies to the acetylcholine receptor (AChR) yield “almost perfect specificity” for myasthenia gravis. Other antibodies in use or under study to confirm this diagnosis include muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), agrin, and cortactin.

The recently completed International Thymectomy Trial, which followed 126 patients for three years, found that those randomly assigned to transsternal thymectomy plus prednisone versus prednisone alone had significantly improved clinical outcomes, as measured on the Quantitative Myasthenia Gravis scale. Patients also required less prednisone, 44 mg versus 60 mg (alternate days), and fewer patients in the thymectomy group required azathioprine (17% versus 48%) or were hospitalized for exacerbations (9% versus 37%).

“Up until this study, nobody was completely sure this treatment worked,” Dr. Pascuzzi said.

Lambert-Eaton Syndrome

In the second case, a woman presented with a six-month history of falling down after her legs gave out on her. She also complained of dry mouth and, on examination, had proximal weakness and no muscle stretch reflexes.

Serology and EMG testing confirmed Lambert-Eaton myasthenic syndrome, a paraneoplastic syndrome. Half the patients with this syndrome have small cell carcinoma, Dr. Pascuzzi said, usually lung, due to smoking. In 64% of cases, the SOX1 antibody is positive.

Treatment approaches include treating the cancer; and 3,4 diaminopyridine, pyridostigmine, and immunotherapy.

Duchenne Muscular Dystrophy

A six-year-old boy with progressive clumsiness was found to have Duchenne muscular dystrophy, a diagnosis with “huge” genetic implications for his three younger brothers, Dr. Pascuzzi said. By age 20, patients are usually on ventilators.

Recently, the FDA granted accelerated approval to the first drug to treat Duchenne muscular dystrophy—Exondys 51 (eteplirsen). The drug “is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13% of the population with Duchenne muscular dystrophy,” the FDA noted.

However, eteplirsen is not without controversy, Dr. Pascuzzi said. “There’s no documented clinical benefit. If you show there is a little more dystrophin being deposited and built in muscle, what does that mean? As of today, nobody knows. So that is an issue I think the FDA Advisory Panel and other people are worried about. And then, at $300,000 a year, it is not a financially insignificant impact.”

As the drug is used, further studies and data “will eventually show that it does or does not have clinical benefit,” Dr. Pascuzzi said. Patients must undergo testing for the mutation. Reported adverse events include balance issues and vomiting.

Amyotrophic Lateral Sclerosis

The third and fourth cases focused on a 53-year-old man with 12 months of progressive decline in speech and swallowing, and a woman with similar symptoms who also would laugh for no apparent reason. Both cases were displaying the pseudobulbar affect of ALS.

About 5% to 10% of all ALS cases are familial and, in 40% to 50%, the most common gene is C9orf72. Less common is the SOD1 gene (20%), with those carrying its A4V mutation generally dying within one year. Other mutations include TDP-43 (5%), and FUS (5%).

Dr. Pascuzzi cautioned that cognitive impairment among patients with ALS can be as high as 40% and cannot usually be detected on a bedside exam. Up to 15% of patients “get a frank, overt, clinically significant dementia, usually a frontotemporal syndrome.”

Treatment approaches include use of multidisciplinary clinics, ankle-foot orthosis, tools for activities of daily living, bilevel positive airway pressure, chin tuck, and power chairs; drugs include riluzole, dextromethorphan/quinidine for pseudobulbar affect, and drugs for spasticity.

He said it is important to address fear, depression, and anxiety in patients with ALS, and not to overlook the caregiver: “We are slowly but surely melting down our caregivers.”

A recent study in Lancet Neurology helped Dr. Pascuzzi and colleagues decide against diaphragm pacing for patients with respiratory insufficiency due to ALS, due to the potential for harm. “I would be cautious about pursuing this,” he said.

Despite the many failed controlled trials over the past 20 years, much investigational work is being done on ALS therapeutics, from injection of antisense molecules to tirasemtiv to stem cells, immune therapy, neuro-protection, and high fat/calorie diet, “so there is reason to be hopeful.”

Stem cell transplantation, in particular, is something he said his patients always ask him about. Two forms, “both important,” have undergone fairly extensive clinical investigation.

In the first, spinal cord-derived neural stem cells are transplanted into the spinal cord.

“The people that drive this work are convinced this is not stem cells that turn into motor neurons and replace lost or failing motor neurons, but instead these are stem cells that provide an environment that is more favorable for sick motor neurons,” Dr. Pascuzzi said. “They secrete nerve growth factors and transport proteins to improve the environment.”

The second approach, autologous stem cell treatment, is a “culture-based method for inducing mesenchymal stem cells to secrete neurotrophic factors,” he said, which has been “shown to be protective in several animal models of neurodegenerative diseases.”

—Debra Hughes

Suggested Reading

DiPALS Writing Committee on behalf of the DiPALS Study Group Collaborators. Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2015;14(9);883-892.

Glass JD, Hertzberg VS, Boulis NM, et al. Transplantation of spinal cord-derived neural stem cells for ALS: analysis of phase 1 and 2 trials. Neurology. 2016;87(4):392-400.

Petrou P, Gothelf Y, Argov Z, et al. Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials. JAMA Neurol. 2016;73(3):337-344.

U.S. Food and Drug Administration. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. FDA News Release. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm. Accessed November 4, 2016.

Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375(6):511-522.

LAS VEGAS—At the American Academy of Neurology’s Fall 2016 Conference, Robert M. Pascuzzi, MD, presented several case videos to illustrate recent advances in caring for patients with rare neuromuscular disorders, including myasthenia gravis, Lambert-Eaton syndrome, Duchenne muscular dystrophy, and amyotrophic lateral sclerosis (ALS). Dr. Pascuzzi is Chair of the Department of Neurology at Indiana University School of Medicine in Indianapolis.

Myasthenia Gravis

The first case, a 55-year-old woman with a six-month history of double vision and swallowing trouble, also expressed the Cogan lid twitch, which is “pathognomonic for myasthenia gravis,” Dr. Pascuzzi said.

“It’s nice to have a test to confirm your clinical suspicions,” he said, noting that antibodies to the acetylcholine receptor (AChR) yield “almost perfect specificity” for myasthenia gravis. Other antibodies in use or under study to confirm this diagnosis include muscle-specific kinase (MuSK), low-density lipoprotein receptor-related protein 4 (LRP4), agrin, and cortactin.

The recently completed International Thymectomy Trial, which followed 126 patients for three years, found that those randomly assigned to transsternal thymectomy plus prednisone versus prednisone alone had significantly improved clinical outcomes, as measured on the Quantitative Myasthenia Gravis scale. Patients also required less prednisone, 44 mg versus 60 mg (alternate days), and fewer patients in the thymectomy group required azathioprine (17% versus 48%) or were hospitalized for exacerbations (9% versus 37%).

“Up until this study, nobody was completely sure this treatment worked,” Dr. Pascuzzi said.

Lambert-Eaton Syndrome

In the second case, a woman presented with a six-month history of falling down after her legs gave out on her. She also complained of dry mouth and, on examination, had proximal weakness and no muscle stretch reflexes.

Serology and EMG testing confirmed Lambert-Eaton myasthenic syndrome, a paraneoplastic syndrome. Half the patients with this syndrome have small cell carcinoma, Dr. Pascuzzi said, usually lung, due to smoking. In 64% of cases, the SOX1 antibody is positive.

Treatment approaches include treating the cancer; and 3,4 diaminopyridine, pyridostigmine, and immunotherapy.

Duchenne Muscular Dystrophy

A six-year-old boy with progressive clumsiness was found to have Duchenne muscular dystrophy, a diagnosis with “huge” genetic implications for his three younger brothers, Dr. Pascuzzi said. By age 20, patients are usually on ventilators.

Recently, the FDA granted accelerated approval to the first drug to treat Duchenne muscular dystrophy—Exondys 51 (eteplirsen). The drug “is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13% of the population with Duchenne muscular dystrophy,” the FDA noted.

However, eteplirsen is not without controversy, Dr. Pascuzzi said. “There’s no documented clinical benefit. If you show there is a little more dystrophin being deposited and built in muscle, what does that mean? As of today, nobody knows. So that is an issue I think the FDA Advisory Panel and other people are worried about. And then, at $300,000 a year, it is not a financially insignificant impact.”

As the drug is used, further studies and data “will eventually show that it does or does not have clinical benefit,” Dr. Pascuzzi said. Patients must undergo testing for the mutation. Reported adverse events include balance issues and vomiting.

Amyotrophic Lateral Sclerosis

The third and fourth cases focused on a 53-year-old man with 12 months of progressive decline in speech and swallowing, and a woman with similar symptoms who also would laugh for no apparent reason. Both cases were displaying the pseudobulbar affect of ALS.

About 5% to 10% of all ALS cases are familial and, in 40% to 50%, the most common gene is C9orf72. Less common is the SOD1 gene (20%), with those carrying its A4V mutation generally dying within one year. Other mutations include TDP-43 (5%), and FUS (5%).

Dr. Pascuzzi cautioned that cognitive impairment among patients with ALS can be as high as 40% and cannot usually be detected on a bedside exam. Up to 15% of patients “get a frank, overt, clinically significant dementia, usually a frontotemporal syndrome.”

Treatment approaches include use of multidisciplinary clinics, ankle-foot orthosis, tools for activities of daily living, bilevel positive airway pressure, chin tuck, and power chairs; drugs include riluzole, dextromethorphan/quinidine for pseudobulbar affect, and drugs for spasticity.

He said it is important to address fear, depression, and anxiety in patients with ALS, and not to overlook the caregiver: “We are slowly but surely melting down our caregivers.”

A recent study in Lancet Neurology helped Dr. Pascuzzi and colleagues decide against diaphragm pacing for patients with respiratory insufficiency due to ALS, due to the potential for harm. “I would be cautious about pursuing this,” he said.

Despite the many failed controlled trials over the past 20 years, much investigational work is being done on ALS therapeutics, from injection of antisense molecules to tirasemtiv to stem cells, immune therapy, neuro-protection, and high fat/calorie diet, “so there is reason to be hopeful.”

Stem cell transplantation, in particular, is something he said his patients always ask him about. Two forms, “both important,” have undergone fairly extensive clinical investigation.

In the first, spinal cord-derived neural stem cells are transplanted into the spinal cord.

“The people that drive this work are convinced this is not stem cells that turn into motor neurons and replace lost or failing motor neurons, but instead these are stem cells that provide an environment that is more favorable for sick motor neurons,” Dr. Pascuzzi said. “They secrete nerve growth factors and transport proteins to improve the environment.”

The second approach, autologous stem cell treatment, is a “culture-based method for inducing mesenchymal stem cells to secrete neurotrophic factors,” he said, which has been “shown to be protective in several animal models of neurodegenerative diseases.”

—Debra Hughes

Suggested Reading

DiPALS Writing Committee on behalf of the DiPALS Study Group Collaborators. Safety and efficacy of diaphragm pacing in patients with respiratory insufficiency due to amyotrophic lateral sclerosis (DiPALS): a multicentre, open-label, randomised controlled trial. Lancet Neurol. 2015;14(9);883-892.

Glass JD, Hertzberg VS, Boulis NM, et al. Transplantation of spinal cord-derived neural stem cells for ALS: analysis of phase 1 and 2 trials. Neurology. 2016;87(4):392-400.

Petrou P, Gothelf Y, Argov Z, et al. Safety and clinical effects of mesenchymal stem cells secreting neurotrophic factor transplantation in patients with amyotrophic lateral sclerosis: results of phase 1/2 and 2a clinical trials. JAMA Neurol. 2016;73(3):337-344.

U.S. Food and Drug Administration. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. FDA News Release. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm. Accessed November 4, 2016.

Wolfe GI, Kaminski HJ, Aban IB, et al. Randomized trial of thymectomy in myasthenia gravis. N Engl J Med. 2016;375(6):511-522.

Background Colorectal cancer (CRC) screening rates remain low, especially among low-income populations.

Objective To determine if a CRC screening intervention (video, brochure) improves knowledge about CRC and CRC screening, attitudes toward screening, and intention to complete CRC screening among average-risk adults with different health literacy skills, seeking medical care at a Federally Qualified Health Center (FQHC).

Methods Average-risk adults (50 years or older) who were not within CRC screening guidelines completed face-to-face pre- and post-intervention interviews that focused on knowledge about CRC and CRC screening, attitudes toward CRC screening, and intention to complete CRC screening.

Results Of the 270 participants, 64% were women, 72% were black/African American, 86% were not married, 79% had an annual household income of <$20,000, and 57% did not have health insurance. Reading levels by Rapid Estimate of Adult Literacy in Medicine health literacy test were: 3rd grade or lower, 17 participants (6.3%); 4th-6th grade, 27 (10.0%); 7th-8th grade, 101 (37.4 %); and high school, 125 (46.3%). CRC screening knowledge mean score improved, and perceived CRC susceptibility and self-efficacy to complete screening significantly increased, irrespective of health literacy (all P < .01). There were no significant changes in other attitudes or intention to complete screening.

Limitations The study was conducted in a single FQHC, so the results may not be generalizable to other health centers or populations of low-income and minority patients.

Conclusion A CRC screening intervention improved CRC screening knowledge and attitudes across levels of health literacy and may be an important strategy for improving CRC screening in the primary care setting. Funding National Cancer Institute K07 CA107079 (Ohio State University) and P30 CA016058 (Behavioral Measurement Shared Resource at The Ohio State University).

Click on the PDF icon at the top of this introduction to read the full article.

Background Colorectal cancer (CRC) screening rates remain low, especially among low-income populations.

Objective To determine if a CRC screening intervention (video, brochure) improves knowledge about CRC and CRC screening, attitudes toward screening, and intention to complete CRC screening among average-risk adults with different health literacy skills, seeking medical care at a Federally Qualified Health Center (FQHC).

Methods Average-risk adults (50 years or older) who were not within CRC screening guidelines completed face-to-face pre- and post-intervention interviews that focused on knowledge about CRC and CRC screening, attitudes toward CRC screening, and intention to complete CRC screening.

Results Of the 270 participants, 64% were women, 72% were black/African American, 86% were not married, 79% had an annual household income of <$20,000, and 57% did not have health insurance. Reading levels by Rapid Estimate of Adult Literacy in Medicine health literacy test were: 3rd grade or lower, 17 participants (6.3%); 4th-6th grade, 27 (10.0%); 7th-8th grade, 101 (37.4 %); and high school, 125 (46.3%). CRC screening knowledge mean score improved, and perceived CRC susceptibility and self-efficacy to complete screening significantly increased, irrespective of health literacy (all P < .01). There were no significant changes in other attitudes or intention to complete screening.

Limitations The study was conducted in a single FQHC, so the results may not be generalizable to other health centers or populations of low-income and minority patients.

Conclusion A CRC screening intervention improved CRC screening knowledge and attitudes across levels of health literacy and may be an important strategy for improving CRC screening in the primary care setting. Funding National Cancer Institute K07 CA107079 (Ohio State University) and P30 CA016058 (Behavioral Measurement Shared Resource at The Ohio State University).

Click on the PDF icon at the top of this introduction to read the full article.

Background Colorectal cancer (CRC) screening rates remain low, especially among low-income populations.

Objective To determine if a CRC screening intervention (video, brochure) improves knowledge about CRC and CRC screening, attitudes toward screening, and intention to complete CRC screening among average-risk adults with different health literacy skills, seeking medical care at a Federally Qualified Health Center (FQHC).

Methods Average-risk adults (50 years or older) who were not within CRC screening guidelines completed face-to-face pre- and post-intervention interviews that focused on knowledge about CRC and CRC screening, attitudes toward CRC screening, and intention to complete CRC screening.

Results Of the 270 participants, 64% were women, 72% were black/African American, 86% were not married, 79% had an annual household income of <$20,000, and 57% did not have health insurance. Reading levels by Rapid Estimate of Adult Literacy in Medicine health literacy test were: 3rd grade or lower, 17 participants (6.3%); 4th-6th grade, 27 (10.0%); 7th-8th grade, 101 (37.4 %); and high school, 125 (46.3%). CRC screening knowledge mean score improved, and perceived CRC susceptibility and self-efficacy to complete screening significantly increased, irrespective of health literacy (all P < .01). There were no significant changes in other attitudes or intention to complete screening.

Limitations The study was conducted in a single FQHC, so the results may not be generalizable to other health centers or populations of low-income and minority patients.

Conclusion A CRC screening intervention improved CRC screening knowledge and attitudes across levels of health literacy and may be an important strategy for improving CRC screening in the primary care setting. Funding National Cancer Institute K07 CA107079 (Ohio State University) and P30 CA016058 (Behavioral Measurement Shared Resource at The Ohio State University).

Click on the PDF icon at the top of this introduction to read the full article.

CHICAGO – Liraglutide reduced the risk of kidney disease progression in patients with type 2 diabetes, a study showed.
 

The latest results from the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial build on the previously reported success of liraglutide in reducing the risk of adverse cardiovascular events in people with type 2 diabetes.

“We now have drugs that not only lower blood sugar but also have an impact on new development of diabetic kidney disease and cardiovascular disease,” said Johannes Mann, MD, of the University of Erlangen-Nürnberg, Erlangen, Germany, in a plenary presentation at the meeting sponsored by the American Society of Nephrology.

The LEADER trial involved people with type 2 diabetes mellitus (mean duration, about 13 years) with a baseline hemoglobin A_1c level greater than or equal to 7%. Some had never taken antidiabetic drugs, and some were taking oral antidiabetic drugs and/or basal/premixed insulin. They were either 50 years of age or older with established cardiovascular disease and chronic kidney disease, or 60 years and older with risk factors for cardiovascular disease.

Exclusion criteria included type 1 diabetes; a history of medication with glucagonlike peptide–1 receptor agonists, dipeptidyl peptidase–4 inhibitors, pramlintide, or rapid-acting insulin; and a family/personal history of multiple endocrine neoplasia type 2 or medullary thyroid cancer.

The 9,340 subjects were randomized in a double-blind fashion to daily subcutaneous injection with 0.6-1.8 mg of liraglutide (4,668) or placebo (4,672) for at least 3.5 years to a maximum treatment time of 5 years. The mean follow-up was 3.8 years.

At baseline, microalbuminuria had been diagnosed in 26.4% and 26.6% of those randomized to liraglutide or placebo, respectively. The respective baseline rates of macroalbuminuria were 10% and 11%. An estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m² was present in 23.9% of the liraglutide group and 22.3% of the control group.

In this analysis of the LEADER results, the primary renal outcome was a composite of the development of macroalbuminuria, doubling of serum creatinine, end-stage renal disease, or renal death. Liraglutide was superior to placebo in delaying the time to the primary outcome (hazard ratio, 0.78; 95% confidence interval, 0.67-0.92; P equal to .003). The outcome was driven by the reduction in development of macroalbuminuria (HR, 0.74; 95% CI, 0.60-0.91; P = .004), with treatment not being significantly effective for doubling of serum creatinine (HR, 0.89; 95% CI, 0.67-1.19) or the need for dialysis (HR, 0.87; 95% CI, 0.61-1.24).

The eGFR declined less in the liraglutide arm. The renal protection of the drug was restricted to subjects with a baseline eGFR of 30-59 mL/min per 1.73 m². Liragutide was not associated with an increased risk of adverse renal events.

The latest results extend the potential indications of the therapeutic prowess of liraglutide in type 2 diabetes patients with chronic kidney disease, with the caveat that the significance of the primary outcome was due to macroalbuminuria rather than the arguably more important outcomes of doubling of serum creatinine and development of end-stage renal disease.

The trial was sponsored and funded by Novo Nordisk, the maker of liraglutide (Victoza) and the National Institutes of Health. Dr. Mann disclosed financial relationships with various drug companies, including Novo Nordisk.

CHICAGO – Liraglutide reduced the risk of kidney disease progression in patients with type 2 diabetes, a study showed.
 

The latest results from the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial build on the previously reported success of liraglutide in reducing the risk of adverse cardiovascular events in people with type 2 diabetes.

“We now have drugs that not only lower blood sugar but also have an impact on new development of diabetic kidney disease and cardiovascular disease,” said Johannes Mann, MD, of the University of Erlangen-Nürnberg, Erlangen, Germany, in a plenary presentation at the meeting sponsored by the American Society of Nephrology.

The LEADER trial involved people with type 2 diabetes mellitus (mean duration, about 13 years) with a baseline hemoglobin A_1c level greater than or equal to 7%. Some had never taken antidiabetic drugs, and some were taking oral antidiabetic drugs and/or basal/premixed insulin. They were either 50 years of age or older with established cardiovascular disease and chronic kidney disease, or 60 years and older with risk factors for cardiovascular disease.

Exclusion criteria included type 1 diabetes; a history of medication with glucagonlike peptide–1 receptor agonists, dipeptidyl peptidase–4 inhibitors, pramlintide, or rapid-acting insulin; and a family/personal history of multiple endocrine neoplasia type 2 or medullary thyroid cancer.

The 9,340 subjects were randomized in a double-blind fashion to daily subcutaneous injection with 0.6-1.8 mg of liraglutide (4,668) or placebo (4,672) for at least 3.5 years to a maximum treatment time of 5 years. The mean follow-up was 3.8 years.

At baseline, microalbuminuria had been diagnosed in 26.4% and 26.6% of those randomized to liraglutide or placebo, respectively. The respective baseline rates of macroalbuminuria were 10% and 11%. An estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m² was present in 23.9% of the liraglutide group and 22.3% of the control group.

In this analysis of the LEADER results, the primary renal outcome was a composite of the development of macroalbuminuria, doubling of serum creatinine, end-stage renal disease, or renal death. Liraglutide was superior to placebo in delaying the time to the primary outcome (hazard ratio, 0.78; 95% confidence interval, 0.67-0.92; P equal to .003). The outcome was driven by the reduction in development of macroalbuminuria (HR, 0.74; 95% CI, 0.60-0.91; P = .004), with treatment not being significantly effective for doubling of serum creatinine (HR, 0.89; 95% CI, 0.67-1.19) or the need for dialysis (HR, 0.87; 95% CI, 0.61-1.24).

The eGFR declined less in the liraglutide arm. The renal protection of the drug was restricted to subjects with a baseline eGFR of 30-59 mL/min per 1.73 m². Liragutide was not associated with an increased risk of adverse renal events.

The latest results extend the potential indications of the therapeutic prowess of liraglutide in type 2 diabetes patients with chronic kidney disease, with the caveat that the significance of the primary outcome was due to macroalbuminuria rather than the arguably more important outcomes of doubling of serum creatinine and development of end-stage renal disease.

The trial was sponsored and funded by Novo Nordisk, the maker of liraglutide (Victoza) and the National Institutes of Health. Dr. Mann disclosed financial relationships with various drug companies, including Novo Nordisk.

CHICAGO – Liraglutide reduced the risk of kidney disease progression in patients with type 2 diabetes, a study showed.
 

The latest results from the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial build on the previously reported success of liraglutide in reducing the risk of adverse cardiovascular events in people with type 2 diabetes.

“We now have drugs that not only lower blood sugar but also have an impact on new development of diabetic kidney disease and cardiovascular disease,” said Johannes Mann, MD, of the University of Erlangen-Nürnberg, Erlangen, Germany, in a plenary presentation at the meeting sponsored by the American Society of Nephrology.

The LEADER trial involved people with type 2 diabetes mellitus (mean duration, about 13 years) with a baseline hemoglobin A_1c level greater than or equal to 7%. Some had never taken antidiabetic drugs, and some were taking oral antidiabetic drugs and/or basal/premixed insulin. They were either 50 years of age or older with established cardiovascular disease and chronic kidney disease, or 60 years and older with risk factors for cardiovascular disease.

Exclusion criteria included type 1 diabetes; a history of medication with glucagonlike peptide–1 receptor agonists, dipeptidyl peptidase–4 inhibitors, pramlintide, or rapid-acting insulin; and a family/personal history of multiple endocrine neoplasia type 2 or medullary thyroid cancer.

The 9,340 subjects were randomized in a double-blind fashion to daily subcutaneous injection with 0.6-1.8 mg of liraglutide (4,668) or placebo (4,672) for at least 3.5 years to a maximum treatment time of 5 years. The mean follow-up was 3.8 years.

At baseline, microalbuminuria had been diagnosed in 26.4% and 26.6% of those randomized to liraglutide or placebo, respectively. The respective baseline rates of macroalbuminuria were 10% and 11%. An estimated glomerular filtration rate (eGFR) less than 60 mL/min per 1.73 m² was present in 23.9% of the liraglutide group and 22.3% of the control group.

In this analysis of the LEADER results, the primary renal outcome was a composite of the development of macroalbuminuria, doubling of serum creatinine, end-stage renal disease, or renal death. Liraglutide was superior to placebo in delaying the time to the primary outcome (hazard ratio, 0.78; 95% confidence interval, 0.67-0.92; P equal to .003). The outcome was driven by the reduction in development of macroalbuminuria (HR, 0.74; 95% CI, 0.60-0.91; P = .004), with treatment not being significantly effective for doubling of serum creatinine (HR, 0.89; 95% CI, 0.67-1.19) or the need for dialysis (HR, 0.87; 95% CI, 0.61-1.24).

The eGFR declined less in the liraglutide arm. The renal protection of the drug was restricted to subjects with a baseline eGFR of 30-59 mL/min per 1.73 m². Liragutide was not associated with an increased risk of adverse renal events.

The latest results extend the potential indications of the therapeutic prowess of liraglutide in type 2 diabetes patients with chronic kidney disease, with the caveat that the significance of the primary outcome was due to macroalbuminuria rather than the arguably more important outcomes of doubling of serum creatinine and development of end-stage renal disease.

The trial was sponsored and funded by Novo Nordisk, the maker of liraglutide (Victoza) and the National Institutes of Health. Dr. Mann disclosed financial relationships with various drug companies, including Novo Nordisk.

This October, CMS released the final rule implementing the provisions of the Medicare Access and CHIP Reauthorization Act (MACRA). AGA is reviewing the 2,398-page regulation and will release a summary of key provisions impacting gastroenterologists in the coming weeks.

• When do changes take effect? Services provided beginning on Jan. 1, 2017, will directly impact reimbursement provided in 2019, the first year in which the MIPS program and APMs are effective.

• What should I do right now? AGA’s MACRA resource center (www.gastro.org/MACRA) provides customized advice based on your practice situation.

• What’s next? Over the coming weeks and months, we will provide detailed information and resources to help practices prepare for the upcoming policy and delivery changes.

Join AGA for our upcoming MACRA webinar series to hear from experts about how MACRA will affect you and your practice. Stay tuned for more information about dates and time. Keep reading below for an overview of the final rule and how it will affect your practice.
 

Final rule overview

• MACRA implementation will not be delayed. The first performance period begins Jan. 1, 2017, which CMS describes as a “transition year.” However, the final rule provides additional details on CMS’ plan to allow physicians to pick their pace of participation under MIPS (see below).

• Merit-based Incentive Programs (MIPS). CMS lowered the cost performance category to 0% in the 2017 transition period and gave clinicians three reporting options under MIPS and one under Advanced Alternative Payment Models (APMs).

• Option one: Report to MIPS for a full 90-day period or full year on quality, clinical performance improvement activities (CPIA), and advancing care (EHR), and maximize the chance to qualify for positive payment adjustments.

• Option two: Report less than a year, but for the full 90-day period on one quality measure, more than one CPIA, or more than the required measures in advancing care information to avoid penalties and receive a possible positive update.

• Option three: Report one quality measure, one CPIA, or report measures of advancing care to avoid penalty.

• Option four: Join an Advanced APM (see below).

Bottom line: If you do not report at least some data in 2017, you will be penalized.

This October, CMS released the final rule implementing the provisions of the Medicare Access and CHIP Reauthorization Act (MACRA). AGA is reviewing the 2,398-page regulation and will release a summary of key provisions impacting gastroenterologists in the coming weeks.

• When do changes take effect? Services provided beginning on Jan. 1, 2017, will directly impact reimbursement provided in 2019, the first year in which the MIPS program and APMs are effective.

• What should I do right now? AGA’s MACRA resource center (www.gastro.org/MACRA) provides customized advice based on your practice situation.

• What’s next? Over the coming weeks and months, we will provide detailed information and resources to help practices prepare for the upcoming policy and delivery changes.

Join AGA for our upcoming MACRA webinar series to hear from experts about how MACRA will affect you and your practice. Stay tuned for more information about dates and time. Keep reading below for an overview of the final rule and how it will affect your practice.
 

Final rule overview

• MACRA implementation will not be delayed. The first performance period begins Jan. 1, 2017, which CMS describes as a “transition year.” However, the final rule provides additional details on CMS’ plan to allow physicians to pick their pace of participation under MIPS (see below).

• Merit-based Incentive Programs (MIPS). CMS lowered the cost performance category to 0% in the 2017 transition period and gave clinicians three reporting options under MIPS and one under Advanced Alternative Payment Models (APMs).

• Option one: Report to MIPS for a full 90-day period or full year on quality, clinical performance improvement activities (CPIA), and advancing care (EHR), and maximize the chance to qualify for positive payment adjustments.

• Option two: Report less than a year, but for the full 90-day period on one quality measure, more than one CPIA, or more than the required measures in advancing care information to avoid penalties and receive a possible positive update.

• Option three: Report one quality measure, one CPIA, or report measures of advancing care to avoid penalty.

• Option four: Join an Advanced APM (see below).

Bottom line: If you do not report at least some data in 2017, you will be penalized.

This October, CMS released the final rule implementing the provisions of the Medicare Access and CHIP Reauthorization Act (MACRA). AGA is reviewing the 2,398-page regulation and will release a summary of key provisions impacting gastroenterologists in the coming weeks.

• When do changes take effect? Services provided beginning on Jan. 1, 2017, will directly impact reimbursement provided in 2019, the first year in which the MIPS program and APMs are effective.

• What should I do right now? AGA’s MACRA resource center (www.gastro.org/MACRA) provides customized advice based on your practice situation.

• What’s next? Over the coming weeks and months, we will provide detailed information and resources to help practices prepare for the upcoming policy and delivery changes.

Join AGA for our upcoming MACRA webinar series to hear from experts about how MACRA will affect you and your practice. Stay tuned for more information about dates and time. Keep reading below for an overview of the final rule and how it will affect your practice.
 

Final rule overview

• MACRA implementation will not be delayed. The first performance period begins Jan. 1, 2017, which CMS describes as a “transition year.” However, the final rule provides additional details on CMS’ plan to allow physicians to pick their pace of participation under MIPS (see below).

• Merit-based Incentive Programs (MIPS). CMS lowered the cost performance category to 0% in the 2017 transition period and gave clinicians three reporting options under MIPS and one under Advanced Alternative Payment Models (APMs).

• Option one: Report to MIPS for a full 90-day period or full year on quality, clinical performance improvement activities (CPIA), and advancing care (EHR), and maximize the chance to qualify for positive payment adjustments.

• Option two: Report less than a year, but for the full 90-day period on one quality measure, more than one CPIA, or more than the required measures in advancing care information to avoid penalties and receive a possible positive update.

• Option three: Report one quality measure, one CPIA, or report measures of advancing care to avoid penalty.

• Option four: Join an Advanced APM (see below).

Bottom line: If you do not report at least some data in 2017, you will be penalized.

AGA’s gold-standard guidelines, clinical support tools, podcasts, and videos are now available for download via the AGA Clinical Guidelines App, part of AGA’s App Central (http://www.gastro.org/on-demand/aga-app-central). The AGA Clinical Guidelines App offers a quick snapshot of key recommendations, and allows you to input information in a step-by-step format to help you make the most informed decisions possible.

You can even take notes and bookmark information for future reference and quicker decision making.

Only the highest-quality scientific evidence is used to develop AGA’s guidelines. The app currently offers guidelines on:

• Hepatitis B Reactivation.

• Drug Therapy for Crohn’s.

• Constipation.

• IBS Drug Management.

• Colonoscopy after Polypectomy.

• Pancreatic Cysts.

Download the the AGA Clinical Guidelines App and AGA App Central on the Apple App Store or Google Play.

AGA’s gold-standard guidelines, clinical support tools, podcasts, and videos are now available for download via the AGA Clinical Guidelines App, part of AGA’s App Central (http://www.gastro.org/on-demand/aga-app-central). The AGA Clinical Guidelines App offers a quick snapshot of key recommendations, and allows you to input information in a step-by-step format to help you make the most informed decisions possible.

You can even take notes and bookmark information for future reference and quicker decision making.

Only the highest-quality scientific evidence is used to develop AGA’s guidelines. The app currently offers guidelines on:

• Hepatitis B Reactivation.

• Drug Therapy for Crohn’s.

• Constipation.

• IBS Drug Management.

• Colonoscopy after Polypectomy.

• Pancreatic Cysts.

Download the the AGA Clinical Guidelines App and AGA App Central on the Apple App Store or Google Play.

AGA’s gold-standard guidelines, clinical support tools, podcasts, and videos are now available for download via the AGA Clinical Guidelines App, part of AGA’s App Central (http://www.gastro.org/on-demand/aga-app-central). The AGA Clinical Guidelines App offers a quick snapshot of key recommendations, and allows you to input information in a step-by-step format to help you make the most informed decisions possible.

You can even take notes and bookmark information for future reference and quicker decision making.

Only the highest-quality scientific evidence is used to develop AGA’s guidelines. The app currently offers guidelines on:

• Hepatitis B Reactivation.

• Drug Therapy for Crohn’s.

• Constipation.

• IBS Drug Management.

• Colonoscopy after Polypectomy.

• Pancreatic Cysts.

Download the the AGA Clinical Guidelines App and AGA App Central on the Apple App Store or Google Play.