Neil Osterweil

BOSTON – A nonsteroidal investigational drug that acts on the glucocorticoid receptor was superior to placebo and noninferior to higher-dose prednisone in adults with rheumatoid arthritis, investigators report.

The drug, prosaically labeled PF-04171327, is a dissociated agonist of the glucocorticoid receptor, lending it the handy acronym DAGR (pronounced “dagger.”). In a phase II safety and efficacy trial, 10-mg and 15-mg daily doses of DAGR were superior in efficacy to placebo at improving rheumatoid arthritis (RA) disease activity scores, and the drug was comparable in efficacy to prednisone at a 10-mg daily dose but with effects similar to 5 mg prednisone on bone formation and glucose markers, said Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant based in Portola Valley, Calif.

“Suppression of plasma cortisol was observed with DAGR 5, 10, and 15 mg versus partial suppression with prednisone 5 and 10 mg. No clinical symptoms of adrenal insufficiency were reported at any time, and rapid recovery of suppression of the HPA [hypothalamic-pituitary-adrenal] axis was evident by week 13 after taper,” she said at a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In preclinical studies, DAGR was shown to have potent anti-inflammatory activity similar to glucocorticoids such as prednisone but with fewer potential adverse events, and phase I trials in healthy volunteers indicated that it was safe. The drug was also shown to have efficacy against RA in a phase IIa trial, Dr. Strand said.

A seven-arm study

In the current study, 323 patients were randomly assigned to receive DAGR in doses of 1 mg (45 patients), 5 mg (47), 10 mg (45), 15 mg (48); prednisone in doses of 5 mg (45) or 10 mg (46); or placebo (47). The study measured efficacy by ACR 20 criteria in which patients must have at least 20% fewer tender joints and at least 20% fewer swollen joints, plus at least a 20% improvement in at least three of five areas: patient and physician rated global assessment of RA, patient pain and physical functioning self-assessments, and erythrocyte sedimentation rate or C-reactive protein results.

At 8 weeks, ACR 20 responses by nonresponder imputation were seen in 78% of patients on the 10 mg DAGR dose, compared with 72% on 10 mg prednisone, 68% on 15 mg DAGR, 60% on 5 mg DAGR, 44% on 1 mg DAGR, 51% on 5 mg prednisone, and 38% on placebo. Similarly proportioned but smaller responses were seen for ACR 50 and ACR 70 measures.

Effects on bone formation biomarkers

An analysis of the effects of DAGR and prednisone on bone formation biomarkers showed that the experimental agent at doses of 1, 5, and 10 mg was noninferior to 5 mg prednisone as measured by procollagen type 1 N-terminal propeptide (P1NP), and that DAGR at all four dose levels tested was noninferior to 5 mg prednisone as measured by osteocalcin.

DAGR at the three lowest dose levels was also noninferior to 5 mg prednisone, according to the bone resorption biomarker type I collagen N-telopeptide related to creatinine (uNTX/uCr), and 5 mg DAGR was noninferior to the comparable prednisone dose for the resorption biomarker serum C-terminal cross-linking telopeptide of type I collagen (sCTX).

DAGR effect on blood glucose and cortisol

DAGR at all four dose levels was also comparable to 5 mg prednisone in the mean change from baseline to week 8 in hemoglobin A_1C in the study population, which was largely comprised of patients without diabetes.

Where DAGR differed from prednisone at both the 5- and 10-mg doses, however, was in its effect on cortisol suppression. The experimental drug at 5-, 10-, and 15-mg doses was found to suppress cortisol significantly more than did both doses of prednisone, which were associated with only partial cortisol suppression. An adrenocorticotropic hormone (ACTH) stimulation test at week 13 showed rapid recovery of HPA axis suppression in more than 95% of all patients, with the remaining patients recovering by week 15, except for two patients who were lost to follow-up.

Treatment adverse events occurred in 20%, 19%, 22%, and 18% of patients on DAGR (from lowest to highest dose), compared with 16% on 5 mg prednisone, 19% on 10 mg prednisone, and 17% of patients on placebo. There were five serious adverse events among all patients on DAGR, three among patients on prednisone, and two among placebo controls.

The findings warrant further evaluation of DAGR as an alternative to prednisone in the treatment of patients with autoimmune disease, Dr. Strand said.

The study was funded by Pfizer. Dr. Strand disclosed serving as a consultant and advisory board member to Pfizer and several other companies.

BOSTON – A nonsteroidal investigational drug that acts on the glucocorticoid receptor was superior to placebo and noninferior to higher-dose prednisone in adults with rheumatoid arthritis, investigators report.

The drug, prosaically labeled PF-04171327, is a dissociated agonist of the glucocorticoid receptor, lending it the handy acronym DAGR (pronounced “dagger.”). In a phase II safety and efficacy trial, 10-mg and 15-mg daily doses of DAGR were superior in efficacy to placebo at improving rheumatoid arthritis (RA) disease activity scores, and the drug was comparable in efficacy to prednisone at a 10-mg daily dose but with effects similar to 5 mg prednisone on bone formation and glucose markers, said Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant based in Portola Valley, Calif.

“Suppression of plasma cortisol was observed with DAGR 5, 10, and 15 mg versus partial suppression with prednisone 5 and 10 mg. No clinical symptoms of adrenal insufficiency were reported at any time, and rapid recovery of suppression of the HPA [hypothalamic-pituitary-adrenal] axis was evident by week 13 after taper,” she said at a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In preclinical studies, DAGR was shown to have potent anti-inflammatory activity similar to glucocorticoids such as prednisone but with fewer potential adverse events, and phase I trials in healthy volunteers indicated that it was safe. The drug was also shown to have efficacy against RA in a phase IIa trial, Dr. Strand said.

A seven-arm study

In the current study, 323 patients were randomly assigned to receive DAGR in doses of 1 mg (45 patients), 5 mg (47), 10 mg (45), 15 mg (48); prednisone in doses of 5 mg (45) or 10 mg (46); or placebo (47). The study measured efficacy by ACR 20 criteria in which patients must have at least 20% fewer tender joints and at least 20% fewer swollen joints, plus at least a 20% improvement in at least three of five areas: patient and physician rated global assessment of RA, patient pain and physical functioning self-assessments, and erythrocyte sedimentation rate or C-reactive protein results.

At 8 weeks, ACR 20 responses by nonresponder imputation were seen in 78% of patients on the 10 mg DAGR dose, compared with 72% on 10 mg prednisone, 68% on 15 mg DAGR, 60% on 5 mg DAGR, 44% on 1 mg DAGR, 51% on 5 mg prednisone, and 38% on placebo. Similarly proportioned but smaller responses were seen for ACR 50 and ACR 70 measures.

Effects on bone formation biomarkers

An analysis of the effects of DAGR and prednisone on bone formation biomarkers showed that the experimental agent at doses of 1, 5, and 10 mg was noninferior to 5 mg prednisone as measured by procollagen type 1 N-terminal propeptide (P1NP), and that DAGR at all four dose levels tested was noninferior to 5 mg prednisone as measured by osteocalcin.

DAGR at the three lowest dose levels was also noninferior to 5 mg prednisone, according to the bone resorption biomarker type I collagen N-telopeptide related to creatinine (uNTX/uCr), and 5 mg DAGR was noninferior to the comparable prednisone dose for the resorption biomarker serum C-terminal cross-linking telopeptide of type I collagen (sCTX).

DAGR effect on blood glucose and cortisol

DAGR at all four dose levels was also comparable to 5 mg prednisone in the mean change from baseline to week 8 in hemoglobin A_1C in the study population, which was largely comprised of patients without diabetes.

Where DAGR differed from prednisone at both the 5- and 10-mg doses, however, was in its effect on cortisol suppression. The experimental drug at 5-, 10-, and 15-mg doses was found to suppress cortisol significantly more than did both doses of prednisone, which were associated with only partial cortisol suppression. An adrenocorticotropic hormone (ACTH) stimulation test at week 13 showed rapid recovery of HPA axis suppression in more than 95% of all patients, with the remaining patients recovering by week 15, except for two patients who were lost to follow-up.

Treatment adverse events occurred in 20%, 19%, 22%, and 18% of patients on DAGR (from lowest to highest dose), compared with 16% on 5 mg prednisone, 19% on 10 mg prednisone, and 17% of patients on placebo. There were five serious adverse events among all patients on DAGR, three among patients on prednisone, and two among placebo controls.

The findings warrant further evaluation of DAGR as an alternative to prednisone in the treatment of patients with autoimmune disease, Dr. Strand said.

The study was funded by Pfizer. Dr. Strand disclosed serving as a consultant and advisory board member to Pfizer and several other companies.

BOSTON – A nonsteroidal investigational drug that acts on the glucocorticoid receptor was superior to placebo and noninferior to higher-dose prednisone in adults with rheumatoid arthritis, investigators report.

The drug, prosaically labeled PF-04171327, is a dissociated agonist of the glucocorticoid receptor, lending it the handy acronym DAGR (pronounced “dagger.”). In a phase II safety and efficacy trial, 10-mg and 15-mg daily doses of DAGR were superior in efficacy to placebo at improving rheumatoid arthritis (RA) disease activity scores, and the drug was comparable in efficacy to prednisone at a 10-mg daily dose but with effects similar to 5 mg prednisone on bone formation and glucose markers, said Dr. Vibeke Strand, a rheumatologist and biopharmaceutical consultant based in Portola Valley, Calif.

“Suppression of plasma cortisol was observed with DAGR 5, 10, and 15 mg versus partial suppression with prednisone 5 and 10 mg. No clinical symptoms of adrenal insufficiency were reported at any time, and rapid recovery of suppression of the HPA [hypothalamic-pituitary-adrenal] axis was evident by week 13 after taper,” she said at a late-breaking abstract session at the annual meeting of the American College of Rheumatology.

In preclinical studies, DAGR was shown to have potent anti-inflammatory activity similar to glucocorticoids such as prednisone but with fewer potential adverse events, and phase I trials in healthy volunteers indicated that it was safe. The drug was also shown to have efficacy against RA in a phase IIa trial, Dr. Strand said.

A seven-arm study

In the current study, 323 patients were randomly assigned to receive DAGR in doses of 1 mg (45 patients), 5 mg (47), 10 mg (45), 15 mg (48); prednisone in doses of 5 mg (45) or 10 mg (46); or placebo (47). The study measured efficacy by ACR 20 criteria in which patients must have at least 20% fewer tender joints and at least 20% fewer swollen joints, plus at least a 20% improvement in at least three of five areas: patient and physician rated global assessment of RA, patient pain and physical functioning self-assessments, and erythrocyte sedimentation rate or C-reactive protein results.

At 8 weeks, ACR 20 responses by nonresponder imputation were seen in 78% of patients on the 10 mg DAGR dose, compared with 72% on 10 mg prednisone, 68% on 15 mg DAGR, 60% on 5 mg DAGR, 44% on 1 mg DAGR, 51% on 5 mg prednisone, and 38% on placebo. Similarly proportioned but smaller responses were seen for ACR 50 and ACR 70 measures.

Effects on bone formation biomarkers

An analysis of the effects of DAGR and prednisone on bone formation biomarkers showed that the experimental agent at doses of 1, 5, and 10 mg was noninferior to 5 mg prednisone as measured by procollagen type 1 N-terminal propeptide (P1NP), and that DAGR at all four dose levels tested was noninferior to 5 mg prednisone as measured by osteocalcin.

DAGR at the three lowest dose levels was also noninferior to 5 mg prednisone, according to the bone resorption biomarker type I collagen N-telopeptide related to creatinine (uNTX/uCr), and 5 mg DAGR was noninferior to the comparable prednisone dose for the resorption biomarker serum C-terminal cross-linking telopeptide of type I collagen (sCTX).

DAGR effect on blood glucose and cortisol

DAGR at all four dose levels was also comparable to 5 mg prednisone in the mean change from baseline to week 8 in hemoglobin A_1C in the study population, which was largely comprised of patients without diabetes.

Where DAGR differed from prednisone at both the 5- and 10-mg doses, however, was in its effect on cortisol suppression. The experimental drug at 5-, 10-, and 15-mg doses was found to suppress cortisol significantly more than did both doses of prednisone, which were associated with only partial cortisol suppression. An adrenocorticotropic hormone (ACTH) stimulation test at week 13 showed rapid recovery of HPA axis suppression in more than 95% of all patients, with the remaining patients recovering by week 15, except for two patients who were lost to follow-up.

Treatment adverse events occurred in 20%, 19%, 22%, and 18% of patients on DAGR (from lowest to highest dose), compared with 16% on 5 mg prednisone, 19% on 10 mg prednisone, and 17% of patients on placebo. There were five serious adverse events among all patients on DAGR, three among patients on prednisone, and two among placebo controls.

The findings warrant further evaluation of DAGR as an alternative to prednisone in the treatment of patients with autoimmune disease, Dr. Strand said.

The study was funded by Pfizer. Dr. Strand disclosed serving as a consultant and advisory board member to Pfizer and several other companies.

BOSTON – Golimumab was significantly better than placebo at reducing disease activity and inflammation in patients with nonradiographic axial spondyloarthritis, but only among those who were positive for disease on MRI or the inflammation marker C-reactive protein.

In the randomized, double-blind, placebo-controlled GO-AHEAD trial of 198 patients with nonradiographic axial spondyloarthritis (nr-axSpA), 71.1% of patients treated with golimumab (Simponi) achieved the primary endpoint of an ASAS 20 at week 16, compared with 40% of patients on placebo (P < .0001), reported Dr. Joachim Sieper of Charité Medical University in Berlin.

But in a subgroup analysis of patients with normal MRI and C-reactive protein (CRP) levels at baseline, there was no significant difference in ASAS 20 responses at week 16, although the number of patients may have been too small to reveal an effect, Dr. Sieper said.

“There was no difference regarding any adverse event, no difference regarding serious adverse events, and also no difference regarding other adverse events, and there were no deaths in this study,” he said at the annual meeting of the American College of Rheumatology.

Golimumab is a tumor necrosis factor–alpha (TNF-alpha) inhibitor approved in the United States for treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe ulcerative colitis.

The phase III trial was a double-blind, placebo-controlled study in 198 patients with a diagnosis of active axSpA according to Assessment of Spondyloarthritis (ASAS) criteria, a disease duration of less than 5 years since symptom onset, and chronic back pain lasting for at least 3 months.

The patients were randomly assigned to receive either golimumab 50 mg every 4 weeks or placebo via subcutaneous injection. A total of 93 patients assigned to golimumab and 97 assigned to placebo completed 16 weeks of therapy.

The primary endpoint was the percentage of patients achieving an ASAS 20, defined as an improvement of at least 20% and absolute improvement of at least 10 units on a 0-100 scale in three of four domains:

• Patient global assessment (by VAS [visual analog scale] global assessment).

• Pain assessment (the average of VAS total and nocturnal pain scores).

• Function (represented by BASFI [Bath Ankylosing Spondylitis Functional Index]).

• Inflammation (the average score of the last two VASs in the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index], concerning morning stiffness intensity and duration), as well as an absence of deterioration (20% or greater worsening) in the potential remaining domain.

As noted before, golimumab met the primary endpoint among all patients, but in a subanalysis the TNF-alpha inhibitor was significantly better than placebo only among patients with evidence of inflammation on MRI or an elevated CRP at baseline (76.9% vs. 37.5%; P < .0001).

Golimumab was also superior to placebo at week 16 on three secondary endpoints: BASDAI 50 (57.7% vs. 30%; P < .0001), ASAS partial remission (33% vs. 18%; P = .0136), and mean change in Spondyloarthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score (–5.3 vs. –0.9; P < .0001).

In an intention-to-treat analysis, more patients on placebo had any adverse events after 60 weeks of follow-up (41.2% for golimumab vs. 47% for placebo). Patients on placebo were also more likely to have an event judged by the investigator to be related to the assigned medication (13.4% vs. 17%). There were no serious infections, opportunistic infections, active tuberculosis, malignancies, serious systemic hypersensitivity reactions, or deaths.

The study was sponsored by Merck Sharp & Dohme. Dr. Sieper disclosed receiving honoraria, speaker fees, and/or consultancy payments from the company. Four of the study coauthors are employees of Merck.

BOSTON – Golimumab was significantly better than placebo at reducing disease activity and inflammation in patients with nonradiographic axial spondyloarthritis, but only among those who were positive for disease on MRI or the inflammation marker C-reactive protein.

In the randomized, double-blind, placebo-controlled GO-AHEAD trial of 198 patients with nonradiographic axial spondyloarthritis (nr-axSpA), 71.1% of patients treated with golimumab (Simponi) achieved the primary endpoint of an ASAS 20 at week 16, compared with 40% of patients on placebo (P < .0001), reported Dr. Joachim Sieper of Charité Medical University in Berlin.

But in a subgroup analysis of patients with normal MRI and C-reactive protein (CRP) levels at baseline, there was no significant difference in ASAS 20 responses at week 16, although the number of patients may have been too small to reveal an effect, Dr. Sieper said.

“There was no difference regarding any adverse event, no difference regarding serious adverse events, and also no difference regarding other adverse events, and there were no deaths in this study,” he said at the annual meeting of the American College of Rheumatology.

Golimumab is a tumor necrosis factor–alpha (TNF-alpha) inhibitor approved in the United States for treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe ulcerative colitis.

The phase III trial was a double-blind, placebo-controlled study in 198 patients with a diagnosis of active axSpA according to Assessment of Spondyloarthritis (ASAS) criteria, a disease duration of less than 5 years since symptom onset, and chronic back pain lasting for at least 3 months.

The patients were randomly assigned to receive either golimumab 50 mg every 4 weeks or placebo via subcutaneous injection. A total of 93 patients assigned to golimumab and 97 assigned to placebo completed 16 weeks of therapy.

The primary endpoint was the percentage of patients achieving an ASAS 20, defined as an improvement of at least 20% and absolute improvement of at least 10 units on a 0-100 scale in three of four domains:

• Patient global assessment (by VAS [visual analog scale] global assessment).

• Pain assessment (the average of VAS total and nocturnal pain scores).

• Function (represented by BASFI [Bath Ankylosing Spondylitis Functional Index]).

• Inflammation (the average score of the last two VASs in the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index], concerning morning stiffness intensity and duration), as well as an absence of deterioration (20% or greater worsening) in the potential remaining domain.

As noted before, golimumab met the primary endpoint among all patients, but in a subanalysis the TNF-alpha inhibitor was significantly better than placebo only among patients with evidence of inflammation on MRI or an elevated CRP at baseline (76.9% vs. 37.5%; P < .0001).

Golimumab was also superior to placebo at week 16 on three secondary endpoints: BASDAI 50 (57.7% vs. 30%; P < .0001), ASAS partial remission (33% vs. 18%; P = .0136), and mean change in Spondyloarthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score (–5.3 vs. –0.9; P < .0001).

In an intention-to-treat analysis, more patients on placebo had any adverse events after 60 weeks of follow-up (41.2% for golimumab vs. 47% for placebo). Patients on placebo were also more likely to have an event judged by the investigator to be related to the assigned medication (13.4% vs. 17%). There were no serious infections, opportunistic infections, active tuberculosis, malignancies, serious systemic hypersensitivity reactions, or deaths.

The study was sponsored by Merck Sharp & Dohme. Dr. Sieper disclosed receiving honoraria, speaker fees, and/or consultancy payments from the company. Four of the study coauthors are employees of Merck.

BOSTON – Golimumab was significantly better than placebo at reducing disease activity and inflammation in patients with nonradiographic axial spondyloarthritis, but only among those who were positive for disease on MRI or the inflammation marker C-reactive protein.

In the randomized, double-blind, placebo-controlled GO-AHEAD trial of 198 patients with nonradiographic axial spondyloarthritis (nr-axSpA), 71.1% of patients treated with golimumab (Simponi) achieved the primary endpoint of an ASAS 20 at week 16, compared with 40% of patients on placebo (P < .0001), reported Dr. Joachim Sieper of Charité Medical University in Berlin.

But in a subgroup analysis of patients with normal MRI and C-reactive protein (CRP) levels at baseline, there was no significant difference in ASAS 20 responses at week 16, although the number of patients may have been too small to reveal an effect, Dr. Sieper said.

“There was no difference regarding any adverse event, no difference regarding serious adverse events, and also no difference regarding other adverse events, and there were no deaths in this study,” he said at the annual meeting of the American College of Rheumatology.

Golimumab is a tumor necrosis factor–alpha (TNF-alpha) inhibitor approved in the United States for treatment of moderate to severe rheumatoid arthritis, active psoriatic arthritis, active ankylosing spondylitis, and moderate to severe ulcerative colitis.

The phase III trial was a double-blind, placebo-controlled study in 198 patients with a diagnosis of active axSpA according to Assessment of Spondyloarthritis (ASAS) criteria, a disease duration of less than 5 years since symptom onset, and chronic back pain lasting for at least 3 months.

The patients were randomly assigned to receive either golimumab 50 mg every 4 weeks or placebo via subcutaneous injection. A total of 93 patients assigned to golimumab and 97 assigned to placebo completed 16 weeks of therapy.

The primary endpoint was the percentage of patients achieving an ASAS 20, defined as an improvement of at least 20% and absolute improvement of at least 10 units on a 0-100 scale in three of four domains:

• Patient global assessment (by VAS [visual analog scale] global assessment).

• Pain assessment (the average of VAS total and nocturnal pain scores).

• Function (represented by BASFI [Bath Ankylosing Spondylitis Functional Index]).

• Inflammation (the average score of the last two VASs in the BASDAI [Bath Ankylosing Spondylitis Disease Activity Index], concerning morning stiffness intensity and duration), as well as an absence of deterioration (20% or greater worsening) in the potential remaining domain.

As noted before, golimumab met the primary endpoint among all patients, but in a subanalysis the TNF-alpha inhibitor was significantly better than placebo only among patients with evidence of inflammation on MRI or an elevated CRP at baseline (76.9% vs. 37.5%; P < .0001).

Golimumab was also superior to placebo at week 16 on three secondary endpoints: BASDAI 50 (57.7% vs. 30%; P < .0001), ASAS partial remission (33% vs. 18%; P = .0136), and mean change in Spondyloarthritis Research Consortium of Canada (SPARCC) MRI sacroiliac joint score (–5.3 vs. –0.9; P < .0001).

In an intention-to-treat analysis, more patients on placebo had any adverse events after 60 weeks of follow-up (41.2% for golimumab vs. 47% for placebo). Patients on placebo were also more likely to have an event judged by the investigator to be related to the assigned medication (13.4% vs. 17%). There were no serious infections, opportunistic infections, active tuberculosis, malignancies, serious systemic hypersensitivity reactions, or deaths.

The study was sponsored by Merck Sharp & Dohme. Dr. Sieper disclosed receiving honoraria, speaker fees, and/or consultancy payments from the company. Four of the study coauthors are employees of Merck.

BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.

Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”

“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.

He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.

The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.

At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.

In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.

In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.

Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.

At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).

There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).

The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.

The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m², compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.

However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.

The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.

The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.

BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.

Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”

“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.

He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.

The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.

At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.

In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.

In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.

Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.

At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).

There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).

The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.

The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m², compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.

However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.

The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.

The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.

BOSTON – It took 10 years to find out that mycophenolate mofetil and azathioprine are comparable as maintenance therapies for patients with lupus nephritis, at least in a European population.

Or as the principal investigator, Dr. Frédéric A. Houssiau of Saint-Luc University Hospital in Brussels, put it, “azathioprine and MMF [mycophenolate mofetil] are equally unefficacious maintenance therapies for lupus nephritis.”

“We really need further research, and new drugs are eagerly awaited,” Dr. Houssiau said at the annual meeting of the American College of Rheumatology.

He presented long-term follow-up results of patients with systemic lupus erythematosus (SLE) and proliferative lupus nephritis enrolled in the MAINTAIN Nephritis Trial.

The investigator-initiated trial compared MMF and azathioprine (AZA) for their ability to prevent renal flares over the long term. The immunosuppressive agents were delivered at target dose of 2 mg/kg per day for AZA or 2 g/day for MMF beginning at week 12 of the study, following induction therapy with glucocorticoids and cyclophosphamide.

At 5-year follow-up, there were fewer flares among patients treated with MMF, but the difference was not significantly superior to AZA.

In the current analysis, the authors sought to determine whether additional follow-up would reveal a difference in efficacy between the two therapies, to see what factors, if any, could predict long-term renal outcomes, and to assess whether inclusion of renal function and urinalysis in the early complete response criteria could improve the prediction of long-term outcomes.

In early 2014, they collected data on patient deaths, renal flares, renal function, and proteinuria at last follow-up, as well as current treatment, cumulated use of immunosuppressive and/or biologic agents, and serious adverse events. They also correlated long-term renal outcomes with each patient’s initial response to therapy during the first year of treatment.

Of the original 105 patients, 13 were lost to follow-up, and 5 had died, including 1 from SLE and 4 from infections. Median follow-up for the remaining 87 patients was 115 months, or 5 months shy of a decade.

At last follow-up, more than half of patients in each group were currently on glucocorticoids, and a nearly equal percentage (55% in the MMF group and 58% in the AZA group) were currently on an immunosuppressant. There were no significant differences in either the need for additional immunosuppressive therapy (36% vs. 47%, respectively), need for additional intravenous cyclophosphamide (12% vs. 22%), or need for rituximab (12% vs. 11%).

There were also no significant between-group differences in the total number of flares (19 vs. 22), proteinuric flares (12 vs. 18), or nephritic flares (6 vs. 4).

The authors also found that baseline data do not predict long-term outcomes. However, a drop in proteinuria from baseline levels early in the course of treatment was significantly predictive of good outcomes at 3, 6, and 12 months. Patients whose last creatinine levels were at or below 120% of baseline had good outcomes, whereas those with levels above 120% of baseline had poor outcomes, Dr. Houssiau said.

The investigators reported better 10-year outcomes among two sets of patients: those with an estimated glomerular filtration rate greater than 60 mL/min per 1.73 m², compared with those with an eGFR less than 60, and patients whose last recorded serum creatinine level was less than 1.4 mg/dL when compared against those with higher values.

However, when they looked at early response criteria sets they found that including renal function and urinalysis did not add predictive value, compared with assessment of proteinuria alone at 12 months.

The findings led the authors to the conclusion that “MMF is not superior to AZA as maintenance therapy in a European population,” Dr. Houssiau said.

The study was an investigator-initiated trial without external support. Dr. Houssiau disclosed occasional consulting for eight different pharmaceutical companies.

BOSTON – Two investigational monoclonal antibodies, each targeting a different cytokine, showed good activity against systemic lupus erythematosus in two separate studies presented at the annual meeting of the American College of Rheumatology.

Sifalimumab, a fully human monoclonal antibody that binds to and neutralizes several different subtypes of interferon-alpha (IFN-alpha), was better than placebo at improving measures of systemic lupus erythematosus (SLE) disease activity in 431 patients enrolled in a phase IIb safety and efficacy study, said Dr. Munther Khamashta of the Graham Hughes Lupus Research Laboratory at King’s College London.

“The primary endpoint, SRI [Systemic Lupus Erythematosus Responder Index] response at 52 weeks, was significant at all doses of sifalimumab, compared with placebo,” he said at the meeting.

There were no major unexpected adverse events with the drug. Investigators have previously documented increased frequency of herpes zoster infections in patients receiving sifalimumab, but the infections respond promptly to antiviral medication, he added.

Sifalimumab is targeted against the type I interferon receptor present on most cells. The specific target is IFN-alpha, the predominant subtype of type I interferons, which have been shown to play a key role in the pathogenesis of SLE.

In the phase II study, 431 adults with moderate to severe active SLE were screened and randomly assigned to receive either sifalimumab in an intravenous infusion every 4 weeks for 1 year at one of three doses – 200 mg, 600 mg, or 1,200 mg – or to placebo on the same schedule. The patients were permitted to receive up to three oral or intramuscular burst and taper steroids up to day 127 of the study.

SRI responses at 52 weeks were seen in 45.4% of patients on placebo, 58.3% of patients on the 200-mg dose (P vs. placebo = .057), 56.5% on the 600-mg dose (P = .094), and 59.8% for the 1,200-mg dose (P = .031).

Dr. Khamashta said that, at the final analysis, the investigators considered a P value less than .098 to be statistically significant because they needed to adjust for a type 1 error rate of 0.1 in the primary endpoint after they performed an interim analysis of the data.

There also were significant improvements in the sifalimumab arms vs. placebo in affected joint counts and in two secondary endpoints at specific doses: improvement in skin rash as measured by CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) and improvement in fatigue.

Anti–interleukin-6 monoclonal antibody tested

An investigational monoclonal antibody targeting a different cytokine, interleukin-6 (IL-6), appeared to reduce the severity of lupus flares, with activity occurring as early as 24 weeks, in a phase II, dose-ranging study of 183 patients with active SLE, said Dr. Daniel J. Wallace, a rheumatologist at Cedars-Sinai Medical Center in Los Angeles.

Although the drug was deemed to be safe at doses of 10 mg and 50 mg given by subcutaneous injection every 8 weeks, there were four deaths attributed to the medication, including two cases of pulmonary embolism and one of cardiorespiratory arrest in patients treated with the 200-mg dose and a suspected pulmonary embolism in a 32-year-old woman treated with the 10-mg dose. The investigators said that Pfizer, the study sponsor, determined that further studies are warranted to better characterize the benefits and risks of the 10-mg and 50-mg doses but will no longer study the 200-mg dose.

The biologic drug, still known only as PF-04236921, is a fully human antibody that binds to and neutralizes the IL-6 ligand rather than the receptor.

Dr. Wallace said that the rationale for targeting IL-6 in lupus is that there are increased IL-6 levels in the disease produced by T and B cells. Hyperactive B cells from SLE patients produce large amounts of immunoglobulins, and blocking IL-6 decreases immunoglobulin and anti-DNA production. A small, open-label study conducted at the National Institutes of Health with an anti-IL-6 receptor showed promising clinical and serologic responses, he noted.

The study reported by Dr. Khamashta was supported by AstraZeneca. He disclosed research grants from Bayer. The study reported by Dr. Wallace was supported by Pfizer. He reported having no relevant disclosures.

BOSTON – Two investigational monoclonal antibodies, each targeting a different cytokine, showed good activity against systemic lupus erythematosus in two separate studies presented at the annual meeting of the American College of Rheumatology.

Sifalimumab, a fully human monoclonal antibody that binds to and neutralizes several different subtypes of interferon-alpha (IFN-alpha), was better than placebo at improving measures of systemic lupus erythematosus (SLE) disease activity in 431 patients enrolled in a phase IIb safety and efficacy study, said Dr. Munther Khamashta of the Graham Hughes Lupus Research Laboratory at King’s College London.

“The primary endpoint, SRI [Systemic Lupus Erythematosus Responder Index] response at 52 weeks, was significant at all doses of sifalimumab, compared with placebo,” he said at the meeting.

There were no major unexpected adverse events with the drug. Investigators have previously documented increased frequency of herpes zoster infections in patients receiving sifalimumab, but the infections respond promptly to antiviral medication, he added.

Sifalimumab is targeted against the type I interferon receptor present on most cells. The specific target is IFN-alpha, the predominant subtype of type I interferons, which have been shown to play a key role in the pathogenesis of SLE.

In the phase II study, 431 adults with moderate to severe active SLE were screened and randomly assigned to receive either sifalimumab in an intravenous infusion every 4 weeks for 1 year at one of three doses – 200 mg, 600 mg, or 1,200 mg – or to placebo on the same schedule. The patients were permitted to receive up to three oral or intramuscular burst and taper steroids up to day 127 of the study.

SRI responses at 52 weeks were seen in 45.4% of patients on placebo, 58.3% of patients on the 200-mg dose (P vs. placebo = .057), 56.5% on the 600-mg dose (P = .094), and 59.8% for the 1,200-mg dose (P = .031).

Dr. Khamashta said that, at the final analysis, the investigators considered a P value less than .098 to be statistically significant because they needed to adjust for a type 1 error rate of 0.1 in the primary endpoint after they performed an interim analysis of the data.

There also were significant improvements in the sifalimumab arms vs. placebo in affected joint counts and in two secondary endpoints at specific doses: improvement in skin rash as measured by CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) and improvement in fatigue.

Anti–interleukin-6 monoclonal antibody tested

An investigational monoclonal antibody targeting a different cytokine, interleukin-6 (IL-6), appeared to reduce the severity of lupus flares, with activity occurring as early as 24 weeks, in a phase II, dose-ranging study of 183 patients with active SLE, said Dr. Daniel J. Wallace, a rheumatologist at Cedars-Sinai Medical Center in Los Angeles.

Although the drug was deemed to be safe at doses of 10 mg and 50 mg given by subcutaneous injection every 8 weeks, there were four deaths attributed to the medication, including two cases of pulmonary embolism and one of cardiorespiratory arrest in patients treated with the 200-mg dose and a suspected pulmonary embolism in a 32-year-old woman treated with the 10-mg dose. The investigators said that Pfizer, the study sponsor, determined that further studies are warranted to better characterize the benefits and risks of the 10-mg and 50-mg doses but will no longer study the 200-mg dose.

The biologic drug, still known only as PF-04236921, is a fully human antibody that binds to and neutralizes the IL-6 ligand rather than the receptor.

Dr. Wallace said that the rationale for targeting IL-6 in lupus is that there are increased IL-6 levels in the disease produced by T and B cells. Hyperactive B cells from SLE patients produce large amounts of immunoglobulins, and blocking IL-6 decreases immunoglobulin and anti-DNA production. A small, open-label study conducted at the National Institutes of Health with an anti-IL-6 receptor showed promising clinical and serologic responses, he noted.

The study reported by Dr. Khamashta was supported by AstraZeneca. He disclosed research grants from Bayer. The study reported by Dr. Wallace was supported by Pfizer. He reported having no relevant disclosures.

BOSTON – Two investigational monoclonal antibodies, each targeting a different cytokine, showed good activity against systemic lupus erythematosus in two separate studies presented at the annual meeting of the American College of Rheumatology.

Sifalimumab, a fully human monoclonal antibody that binds to and neutralizes several different subtypes of interferon-alpha (IFN-alpha), was better than placebo at improving measures of systemic lupus erythematosus (SLE) disease activity in 431 patients enrolled in a phase IIb safety and efficacy study, said Dr. Munther Khamashta of the Graham Hughes Lupus Research Laboratory at King’s College London.

“The primary endpoint, SRI [Systemic Lupus Erythematosus Responder Index] response at 52 weeks, was significant at all doses of sifalimumab, compared with placebo,” he said at the meeting.

There were no major unexpected adverse events with the drug. Investigators have previously documented increased frequency of herpes zoster infections in patients receiving sifalimumab, but the infections respond promptly to antiviral medication, he added.

Sifalimumab is targeted against the type I interferon receptor present on most cells. The specific target is IFN-alpha, the predominant subtype of type I interferons, which have been shown to play a key role in the pathogenesis of SLE.

In the phase II study, 431 adults with moderate to severe active SLE were screened and randomly assigned to receive either sifalimumab in an intravenous infusion every 4 weeks for 1 year at one of three doses – 200 mg, 600 mg, or 1,200 mg – or to placebo on the same schedule. The patients were permitted to receive up to three oral or intramuscular burst and taper steroids up to day 127 of the study.

SRI responses at 52 weeks were seen in 45.4% of patients on placebo, 58.3% of patients on the 200-mg dose (P vs. placebo = .057), 56.5% on the 600-mg dose (P = .094), and 59.8% for the 1,200-mg dose (P = .031).

Dr. Khamashta said that, at the final analysis, the investigators considered a P value less than .098 to be statistically significant because they needed to adjust for a type 1 error rate of 0.1 in the primary endpoint after they performed an interim analysis of the data.

There also were significant improvements in the sifalimumab arms vs. placebo in affected joint counts and in two secondary endpoints at specific doses: improvement in skin rash as measured by CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity Index) and improvement in fatigue.

Anti–interleukin-6 monoclonal antibody tested

An investigational monoclonal antibody targeting a different cytokine, interleukin-6 (IL-6), appeared to reduce the severity of lupus flares, with activity occurring as early as 24 weeks, in a phase II, dose-ranging study of 183 patients with active SLE, said Dr. Daniel J. Wallace, a rheumatologist at Cedars-Sinai Medical Center in Los Angeles.

Although the drug was deemed to be safe at doses of 10 mg and 50 mg given by subcutaneous injection every 8 weeks, there were four deaths attributed to the medication, including two cases of pulmonary embolism and one of cardiorespiratory arrest in patients treated with the 200-mg dose and a suspected pulmonary embolism in a 32-year-old woman treated with the 10-mg dose. The investigators said that Pfizer, the study sponsor, determined that further studies are warranted to better characterize the benefits and risks of the 10-mg and 50-mg doses but will no longer study the 200-mg dose.

The biologic drug, still known only as PF-04236921, is a fully human antibody that binds to and neutralizes the IL-6 ligand rather than the receptor.

Dr. Wallace said that the rationale for targeting IL-6 in lupus is that there are increased IL-6 levels in the disease produced by T and B cells. Hyperactive B cells from SLE patients produce large amounts of immunoglobulins, and blocking IL-6 decreases immunoglobulin and anti-DNA production. A small, open-label study conducted at the National Institutes of Health with an anti-IL-6 receptor showed promising clinical and serologic responses, he noted.

The study reported by Dr. Khamashta was supported by AstraZeneca. He disclosed research grants from Bayer. The study reported by Dr. Wallace was supported by Pfizer. He reported having no relevant disclosures.

BOSTON – Moderately obese patients who either don’t want or don’t qualify for bariatric surgery may be able to benefit from a reversible procedure using an investigational intragastric balloon.

In a randomized controlled trial, patients with a body mass index (BMI) from 30 to 40 kg/m² who were assigned to receive a dual intragastric balloon (ReShape Duo) plus a diet and exercise regimen lost 25% of their excess weight, compared with only 11% of patients assigned to undergo a sham procedure plus diet and exercise, reported Dr. Jaime Ponce, medical director for the Bariatric Surgery program at Hamilton Medical Center in Dalton, Ga., and Memorial Hospital in Chattanooga, Tenn.

Neil Osterweil/Frontline Medical News

“The ReShape procedure is a reversible intervention that can be used in patients with BMI from 30 to 40 who are not ready for surgery or did not qualify for surgery. It was effective, as it showed a 2.2 times greater weight loss, compared with the diet group,” he said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

At 48 weeks, patients sustained on average 65% of the weight loss they had achieved at week 24, he said.

Two-chamber device

The dual intragastric balloon consists of two silicone balloons connected by a flexible shaft to provide migration resistance. The deflated device is inserted over a guide wire into the stomach in a transoral endoscopic procedure. Once in place, the device is inflated with a saline and methylene blue solution by a powered pump, up to a total volume of 750 to 900 cc. The mean duration of the procedure is 8 minutes Dr. Ponce said.

Barring problems, the device is left in place for 6 months and is then emptied, captured with a standard endoscopic snare, and removed, a process that takes a mean of 14 minutes.

Dr. Ponce and colleagues enrolled obese adults with a BMD from 30 to 40 kg/m² and one or more obesity-related comorbidities to undergo either balloon insertion, diet and exercise (187 patients), or a sham procedure plus diet and exercise (139).

All patients had monthly counseling on diet and exercise as per obesity management guidelines from the National Heart, Lung and Blood Institute published in 2000.

The participants were blinded to treatment assignment for 24 weeks, at which time patients in the diet group could exit the study or, if they wished, receive the balloon and continue in the study for an additional 24 weeks. Patients who initially received the balloon remained in the study and continued diet and exercise during the same 24 weeks.

Balloons were successfully inserted in 99.6% of cases, and all inserted balloons were retrieved successfully. Three patients had serious adverse events related to retrieval: one case of pneumonia requiring hospitalization and antibiotics, one contained perforation of the cervical esophagus, also requiring hospitalization and antibiotics, and one proximal esophageal mucosal tear requiring hemostatic clips.

The trial met its primary endpoint of a greater than 7.5% difference between the balloon and control groups, with balloon receivers having a mean excess weight loss of 25.1%, compared with 11.3% for controls (P = .0041) in an intention to treat analysis, and 27.9% vs. 12.3%, respectively, in patients who completed the study (P = .0007).

At 48 weeks, patients initially assigned to receive the balloon had significant improvements in hemoglobin A_1c, cholesterol levels (HDL up, LDL down), systolic and diastolic blood pressures, and waist and hip circumference.

Among all implanted participants, 11.6% had mild to moderate nausea and vomiting on day 3, which gradually declined over the study. In addition, 34.1% had abdominal pain they rated as mild to moderate on a visual analog scale,

The safety analysis, including all 264 patients who received the balloon initially or at week 24, showed no deaths, balloon migration, obstructions, or required surgeries. Most adverse events were gastrointestinal in nature, mild to moderate, and resolved within the first 30 days.

Investigators saw gastric ulcers in 93 of the 264 patients who received the balloon. They determined the cause to be the distal tip of the device contacting the incisural wall, where more than 95% of the ulcers were observed. The manufacturer made minor changes to lower the profile of the tip and make it smoother and softer, resulting a “dramatically reduced ulcer rate and size,” Dr. Ponce said.

In all, 15% of the balloons were retrieved early, 6% after 2 months, associated with ulcers, and 9% within 2 months of insertions because of device intolerance. The authors found shorter patients had significantly fewer problems when the balloons were inflated with 750 cc rather than 900 cc.

The balloons spontaneously deflated in 6% of participants, signaled by the presence of blue-green urine in about two-thirds of these patients. All of the devices in these cases were successfully retrieved without problems, Dr. Ponce said.

Dr. Manoel P. Galvao Neto of the Gastro Obeso Center in São Paulo, Brazil, the invited discussant, commented that the study was well designed and carried out, with a clear methodology and frank assessment of adverse events, and it met all of its primary endpoints.

Excretable balloon

In a separate pilot study, eight patients who swallowed a limited-duration, self-emptying balloon (Elipse) that is excreted through the bowel lost an average of 12% of excess body weight, reported Dr. Evzen Machytka of the department of clinical studies at the University of Ostrava, Czech Republic.

For the trial, investigators used a custom device designed to self-deflate in 6 weeks. The device is packaged in a capsule and is attached to a thin capillary tube. The patient swallows the balloon without endoscopy or anesthesia. The capsule dissolves quickly, and when gastric positioning of the balloon is confirmed with x-rays, the balloon is then filled with 450 mL saline, in a process that takes approximately 15 minutes.

After a prespecified time (6 weeks, in the case of the trial, 3 months in the device intended for market) a self-releasing valve opens, the balloon empties and is then excreted normally, Dr. Machytka said.

In the pilot trial, all eight balloons were safely excreted. One had deflated early because of a manufacturing defect, and one asymptomatic patient withdrew from the study because she “no longer enjoyed eating.” In both cases, the balloons were punctured via endoscopy but not retrieved, and were excreted normally in the stool 4 days later.

The investigators hope to receive marketing approval for the device in 2015, Dr. Machytka said.

BOSTON – Moderately obese patients who either don’t want or don’t qualify for bariatric surgery may be able to benefit from a reversible procedure using an investigational intragastric balloon.

In a randomized controlled trial, patients with a body mass index (BMI) from 30 to 40 kg/m² who were assigned to receive a dual intragastric balloon (ReShape Duo) plus a diet and exercise regimen lost 25% of their excess weight, compared with only 11% of patients assigned to undergo a sham procedure plus diet and exercise, reported Dr. Jaime Ponce, medical director for the Bariatric Surgery program at Hamilton Medical Center in Dalton, Ga., and Memorial Hospital in Chattanooga, Tenn.

Neil Osterweil/Frontline Medical News

“The ReShape procedure is a reversible intervention that can be used in patients with BMI from 30 to 40 who are not ready for surgery or did not qualify for surgery. It was effective, as it showed a 2.2 times greater weight loss, compared with the diet group,” he said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

At 48 weeks, patients sustained on average 65% of the weight loss they had achieved at week 24, he said.

Two-chamber device

The dual intragastric balloon consists of two silicone balloons connected by a flexible shaft to provide migration resistance. The deflated device is inserted over a guide wire into the stomach in a transoral endoscopic procedure. Once in place, the device is inflated with a saline and methylene blue solution by a powered pump, up to a total volume of 750 to 900 cc. The mean duration of the procedure is 8 minutes Dr. Ponce said.

Barring problems, the device is left in place for 6 months and is then emptied, captured with a standard endoscopic snare, and removed, a process that takes a mean of 14 minutes.

Dr. Ponce and colleagues enrolled obese adults with a BMD from 30 to 40 kg/m² and one or more obesity-related comorbidities to undergo either balloon insertion, diet and exercise (187 patients), or a sham procedure plus diet and exercise (139).

All patients had monthly counseling on diet and exercise as per obesity management guidelines from the National Heart, Lung and Blood Institute published in 2000.

The participants were blinded to treatment assignment for 24 weeks, at which time patients in the diet group could exit the study or, if they wished, receive the balloon and continue in the study for an additional 24 weeks. Patients who initially received the balloon remained in the study and continued diet and exercise during the same 24 weeks.

Balloons were successfully inserted in 99.6% of cases, and all inserted balloons were retrieved successfully. Three patients had serious adverse events related to retrieval: one case of pneumonia requiring hospitalization and antibiotics, one contained perforation of the cervical esophagus, also requiring hospitalization and antibiotics, and one proximal esophageal mucosal tear requiring hemostatic clips.

The trial met its primary endpoint of a greater than 7.5% difference between the balloon and control groups, with balloon receivers having a mean excess weight loss of 25.1%, compared with 11.3% for controls (P = .0041) in an intention to treat analysis, and 27.9% vs. 12.3%, respectively, in patients who completed the study (P = .0007).

At 48 weeks, patients initially assigned to receive the balloon had significant improvements in hemoglobin A_1c, cholesterol levels (HDL up, LDL down), systolic and diastolic blood pressures, and waist and hip circumference.

Among all implanted participants, 11.6% had mild to moderate nausea and vomiting on day 3, which gradually declined over the study. In addition, 34.1% had abdominal pain they rated as mild to moderate on a visual analog scale,

The safety analysis, including all 264 patients who received the balloon initially or at week 24, showed no deaths, balloon migration, obstructions, or required surgeries. Most adverse events were gastrointestinal in nature, mild to moderate, and resolved within the first 30 days.

Investigators saw gastric ulcers in 93 of the 264 patients who received the balloon. They determined the cause to be the distal tip of the device contacting the incisural wall, where more than 95% of the ulcers were observed. The manufacturer made minor changes to lower the profile of the tip and make it smoother and softer, resulting a “dramatically reduced ulcer rate and size,” Dr. Ponce said.

In all, 15% of the balloons were retrieved early, 6% after 2 months, associated with ulcers, and 9% within 2 months of insertions because of device intolerance. The authors found shorter patients had significantly fewer problems when the balloons were inflated with 750 cc rather than 900 cc.

The balloons spontaneously deflated in 6% of participants, signaled by the presence of blue-green urine in about two-thirds of these patients. All of the devices in these cases were successfully retrieved without problems, Dr. Ponce said.

Dr. Manoel P. Galvao Neto of the Gastro Obeso Center in São Paulo, Brazil, the invited discussant, commented that the study was well designed and carried out, with a clear methodology and frank assessment of adverse events, and it met all of its primary endpoints.

Excretable balloon

In a separate pilot study, eight patients who swallowed a limited-duration, self-emptying balloon (Elipse) that is excreted through the bowel lost an average of 12% of excess body weight, reported Dr. Evzen Machytka of the department of clinical studies at the University of Ostrava, Czech Republic.

For the trial, investigators used a custom device designed to self-deflate in 6 weeks. The device is packaged in a capsule and is attached to a thin capillary tube. The patient swallows the balloon without endoscopy or anesthesia. The capsule dissolves quickly, and when gastric positioning of the balloon is confirmed with x-rays, the balloon is then filled with 450 mL saline, in a process that takes approximately 15 minutes.

After a prespecified time (6 weeks, in the case of the trial, 3 months in the device intended for market) a self-releasing valve opens, the balloon empties and is then excreted normally, Dr. Machytka said.

In the pilot trial, all eight balloons were safely excreted. One had deflated early because of a manufacturing defect, and one asymptomatic patient withdrew from the study because she “no longer enjoyed eating.” In both cases, the balloons were punctured via endoscopy but not retrieved, and were excreted normally in the stool 4 days later.

The investigators hope to receive marketing approval for the device in 2015, Dr. Machytka said.

BOSTON – Moderately obese patients who either don’t want or don’t qualify for bariatric surgery may be able to benefit from a reversible procedure using an investigational intragastric balloon.

In a randomized controlled trial, patients with a body mass index (BMI) from 30 to 40 kg/m² who were assigned to receive a dual intragastric balloon (ReShape Duo) plus a diet and exercise regimen lost 25% of their excess weight, compared with only 11% of patients assigned to undergo a sham procedure plus diet and exercise, reported Dr. Jaime Ponce, medical director for the Bariatric Surgery program at Hamilton Medical Center in Dalton, Ga., and Memorial Hospital in Chattanooga, Tenn.

Neil Osterweil/Frontline Medical News

“The ReShape procedure is a reversible intervention that can be used in patients with BMI from 30 to 40 who are not ready for surgery or did not qualify for surgery. It was effective, as it showed a 2.2 times greater weight loss, compared with the diet group,” he said at the meeting presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

At 48 weeks, patients sustained on average 65% of the weight loss they had achieved at week 24, he said.

Two-chamber device

The dual intragastric balloon consists of two silicone balloons connected by a flexible shaft to provide migration resistance. The deflated device is inserted over a guide wire into the stomach in a transoral endoscopic procedure. Once in place, the device is inflated with a saline and methylene blue solution by a powered pump, up to a total volume of 750 to 900 cc. The mean duration of the procedure is 8 minutes Dr. Ponce said.

Barring problems, the device is left in place for 6 months and is then emptied, captured with a standard endoscopic snare, and removed, a process that takes a mean of 14 minutes.

Dr. Ponce and colleagues enrolled obese adults with a BMD from 30 to 40 kg/m² and one or more obesity-related comorbidities to undergo either balloon insertion, diet and exercise (187 patients), or a sham procedure plus diet and exercise (139).

All patients had monthly counseling on diet and exercise as per obesity management guidelines from the National Heart, Lung and Blood Institute published in 2000.

The participants were blinded to treatment assignment for 24 weeks, at which time patients in the diet group could exit the study or, if they wished, receive the balloon and continue in the study for an additional 24 weeks. Patients who initially received the balloon remained in the study and continued diet and exercise during the same 24 weeks.

Balloons were successfully inserted in 99.6% of cases, and all inserted balloons were retrieved successfully. Three patients had serious adverse events related to retrieval: one case of pneumonia requiring hospitalization and antibiotics, one contained perforation of the cervical esophagus, also requiring hospitalization and antibiotics, and one proximal esophageal mucosal tear requiring hemostatic clips.

The trial met its primary endpoint of a greater than 7.5% difference between the balloon and control groups, with balloon receivers having a mean excess weight loss of 25.1%, compared with 11.3% for controls (P = .0041) in an intention to treat analysis, and 27.9% vs. 12.3%, respectively, in patients who completed the study (P = .0007).

At 48 weeks, patients initially assigned to receive the balloon had significant improvements in hemoglobin A_1c, cholesterol levels (HDL up, LDL down), systolic and diastolic blood pressures, and waist and hip circumference.

Among all implanted participants, 11.6% had mild to moderate nausea and vomiting on day 3, which gradually declined over the study. In addition, 34.1% had abdominal pain they rated as mild to moderate on a visual analog scale,

The safety analysis, including all 264 patients who received the balloon initially or at week 24, showed no deaths, balloon migration, obstructions, or required surgeries. Most adverse events were gastrointestinal in nature, mild to moderate, and resolved within the first 30 days.

Investigators saw gastric ulcers in 93 of the 264 patients who received the balloon. They determined the cause to be the distal tip of the device contacting the incisural wall, where more than 95% of the ulcers were observed. The manufacturer made minor changes to lower the profile of the tip and make it smoother and softer, resulting a “dramatically reduced ulcer rate and size,” Dr. Ponce said.

In all, 15% of the balloons were retrieved early, 6% after 2 months, associated with ulcers, and 9% within 2 months of insertions because of device intolerance. The authors found shorter patients had significantly fewer problems when the balloons were inflated with 750 cc rather than 900 cc.

The balloons spontaneously deflated in 6% of participants, signaled by the presence of blue-green urine in about two-thirds of these patients. All of the devices in these cases were successfully retrieved without problems, Dr. Ponce said.

Dr. Manoel P. Galvao Neto of the Gastro Obeso Center in São Paulo, Brazil, the invited discussant, commented that the study was well designed and carried out, with a clear methodology and frank assessment of adverse events, and it met all of its primary endpoints.

Excretable balloon

In a separate pilot study, eight patients who swallowed a limited-duration, self-emptying balloon (Elipse) that is excreted through the bowel lost an average of 12% of excess body weight, reported Dr. Evzen Machytka of the department of clinical studies at the University of Ostrava, Czech Republic.

For the trial, investigators used a custom device designed to self-deflate in 6 weeks. The device is packaged in a capsule and is attached to a thin capillary tube. The patient swallows the balloon without endoscopy or anesthesia. The capsule dissolves quickly, and when gastric positioning of the balloon is confirmed with x-rays, the balloon is then filled with 450 mL saline, in a process that takes approximately 15 minutes.

After a prespecified time (6 weeks, in the case of the trial, 3 months in the device intended for market) a self-releasing valve opens, the balloon empties and is then excreted normally, Dr. Machytka said.

In the pilot trial, all eight balloons were safely excreted. One had deflated early because of a manufacturing defect, and one asymptomatic patient withdrew from the study because she “no longer enjoyed eating.” In both cases, the balloons were punctured via endoscopy but not retrieved, and were excreted normally in the stool 4 days later.

The investigators hope to receive marketing approval for the device in 2015, Dr. Machytka said.

BOSTON – Medical residents in the United States appear to understand that cardiopulmonary resuscitation or intubation is highly unlikely to benefit patients with advanced cancers at the end of life, but the majority of residents surveyed said that they do not discuss code-status options or potentially beneficial palliative care with their dying patients.

“This was primarily due to residents’ perceptions of patient autonomy: Residents wanted patients to make their own decisions, without any influence from the doctor, which misses the concept of informed decision making. These incomplete discussions can cause at minimum improper documentation of patients’ wishes, and at most psychological harm, damage to the physician-patient relationship, and the potential for unwanted attempts at resuscitation,” said Dr. David J. Einstein, a resident at Beth Israel Deaconess Medical Center and Tufts Medical Center, both in Boston.

Despite their reluctance to have the discussion, however, the majority of residents said they preferred to discuss code status with patients themselves rather than hand it off to the attending physician, primarily out of a sense that it is their responsibility as physicians. Yet these physicians in training did not seem to feel that they were also responsible for providing guidance to patients, Dr. Einstein said at the Palliative Care in Oncology Symposium.

“We felt that this represented an unmet need in training and practice. Residents and attendings should be providing guidance on all medical interventions, including CPR, and if they aren’t sure what to recommend, then they themselves should be seeking guidance from other experts, before asking a patient to falsely choose between an intervention and death,” he said.

The first discussion of code status – do not resuscitate (DNR) or do not intubate (DNI) – may occur in the hospital, and is often left to a resident physician. Ideally, the physician and patient should discuss the patient’s prognosis, goals for care, evaluation of CPR as a means of meeting those goals, and a recommendation. But many residents lack training in the end-of-life discussion, which can have a significant impact on the quality of the patients’ remaining weeks or months of life.

Nationwide survey

Dr. Einstein and his colleagues conducted a nationwide survey to measure the likelihood that residents would discuss prognostic information and offer recommendations to patients with limited life expectancy. They also sought to determine why residents might be reluctant to provide discussion, and to evaluate their satisfaction with code-status discussions that both they and their attending physicians have conducted.

The survey presented respondents with a hypothetical case of a patient with stage IV adenocarcinoma of the lung metastatic to the brain. The patient, who has disease progression despite receiving first- and second-line therapy, presents to the emergency department with dyspnea and is slightly hypoxemic, but is not in distress. The patient has not previously established a code-status preference.

The investigators contacted 387 residency program directors by mail, 19 of whom agreed to participate and responded. They sent surveys to a total of 1,627 residents, 358 of which were completed and included.

The investigators found that slightly less than half of the respondents said they would share information with the patient about his/her prognosis and the relative benefit of CPR, and more than two-thirds said they would be unlikely to offer a specific recommendation.

“So even in the situation with a clearly declining patient, residents were as likely as not to provide the information needed to make an informed decision, and were far less likely to provide guidance on this decision,” Dr. Einstein said.

Asked the reason for their decisions, 69% of the residents who would not offer a recommendation said that the patient should make his/her own decision without any influence, and 26.5% said that the attending would not want them to offer a recommendation. Nonetheless, only 1.3% of this group said they believed that CPR would offer the patient a reasonable chance of resuscitation.

The majority of respondents who would offer a recommendation (93.5%) said they would recommend DNR and DNI.

Code-status talk a ‘responsibility’

When they were asked whether they would prefer the attending to discuss code status, nearly 70% of respondents disagreed.

Of those residents who said they preferred to retain the code-status discussion, 93.4% said they thought it was part of their responsibility as a physician, and 65.8% said they thought they had sufficient training and knowledge to do it. A minority in this group (2.5%) said that they would be likely to disagree with the attending’s estimate of prognosis, and 4.9% said they thought the attending would not share his/her estimate honestly.

When the authors asked about the residents’ general satisfaction with discussion of code status, “we learned two things: one, the residents are significantly more satisfied with their own discussions than their attendings’ discussions; and two, there is a substantial minority that is dissatisfied with all discussions, and a small number who are actually very satisfied,” Dr. Einstein said.

In a linear regression analysis testing for hypothesized correlations, the investigators found that more-senior residents were more likely to share prognostic information and make recommendations (P = .002). Residents who expressed an interest in hematology/oncology or palliative care specialization were also more likely to offer prognostic information, but not to make a recommendation about code status.

More-senior year of training correlated negatively with satisfaction with both the resident’s own and the attending’s discussion of code status.

“We found substantial dissatisfaction with code-status discussions in general, and we hypothesize that this is due to an internal conflict. When a resident knows that an intervention may be more harmful than beneficial, but thinks that the patient should make their own decision alone, then one may experience substantial frustration, and this would increase as training goes on and one becomes more sure of the outcomes of interventions like CPR,” Dr. Einstein said.

Generation gap

Evoking a potential generation gap between old-school doctors and the up-and-coming young physicians who by statute work fewer hours than their mentors had to, “I’m struck that [residents] don’t trust the attendings. When I was a resident, you didn’t do anything without asking the attending,” said Dr. Michael H. Levy, an invited discussant who is vice chair of medical oncology and director of the pain and palliative care program at Fox Chase Cancer Center, Philadelphia.

“I’m glad that the residents want to do it, but they have the same arrogance/ignorance that they don’t know how, so if we want them to do it, we have to train them,” he said.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. The study was supported in part by the Conquer Cancer Foundation. Dr. Einstein and Dr. Levy reported having no relevant disclosures.

BOSTON – Medical residents in the United States appear to understand that cardiopulmonary resuscitation or intubation is highly unlikely to benefit patients with advanced cancers at the end of life, but the majority of residents surveyed said that they do not discuss code-status options or potentially beneficial palliative care with their dying patients.

“This was primarily due to residents’ perceptions of patient autonomy: Residents wanted patients to make their own decisions, without any influence from the doctor, which misses the concept of informed decision making. These incomplete discussions can cause at minimum improper documentation of patients’ wishes, and at most psychological harm, damage to the physician-patient relationship, and the potential for unwanted attempts at resuscitation,” said Dr. David J. Einstein, a resident at Beth Israel Deaconess Medical Center and Tufts Medical Center, both in Boston.

Despite their reluctance to have the discussion, however, the majority of residents said they preferred to discuss code status with patients themselves rather than hand it off to the attending physician, primarily out of a sense that it is their responsibility as physicians. Yet these physicians in training did not seem to feel that they were also responsible for providing guidance to patients, Dr. Einstein said at the Palliative Care in Oncology Symposium.

“We felt that this represented an unmet need in training and practice. Residents and attendings should be providing guidance on all medical interventions, including CPR, and if they aren’t sure what to recommend, then they themselves should be seeking guidance from other experts, before asking a patient to falsely choose between an intervention and death,” he said.

The first discussion of code status – do not resuscitate (DNR) or do not intubate (DNI) – may occur in the hospital, and is often left to a resident physician. Ideally, the physician and patient should discuss the patient’s prognosis, goals for care, evaluation of CPR as a means of meeting those goals, and a recommendation. But many residents lack training in the end-of-life discussion, which can have a significant impact on the quality of the patients’ remaining weeks or months of life.

Nationwide survey

Dr. Einstein and his colleagues conducted a nationwide survey to measure the likelihood that residents would discuss prognostic information and offer recommendations to patients with limited life expectancy. They also sought to determine why residents might be reluctant to provide discussion, and to evaluate their satisfaction with code-status discussions that both they and their attending physicians have conducted.

The survey presented respondents with a hypothetical case of a patient with stage IV adenocarcinoma of the lung metastatic to the brain. The patient, who has disease progression despite receiving first- and second-line therapy, presents to the emergency department with dyspnea and is slightly hypoxemic, but is not in distress. The patient has not previously established a code-status preference.

The investigators contacted 387 residency program directors by mail, 19 of whom agreed to participate and responded. They sent surveys to a total of 1,627 residents, 358 of which were completed and included.

The investigators found that slightly less than half of the respondents said they would share information with the patient about his/her prognosis and the relative benefit of CPR, and more than two-thirds said they would be unlikely to offer a specific recommendation.

“So even in the situation with a clearly declining patient, residents were as likely as not to provide the information needed to make an informed decision, and were far less likely to provide guidance on this decision,” Dr. Einstein said.

Asked the reason for their decisions, 69% of the residents who would not offer a recommendation said that the patient should make his/her own decision without any influence, and 26.5% said that the attending would not want them to offer a recommendation. Nonetheless, only 1.3% of this group said they believed that CPR would offer the patient a reasonable chance of resuscitation.

The majority of respondents who would offer a recommendation (93.5%) said they would recommend DNR and DNI.

Code-status talk a ‘responsibility’

When they were asked whether they would prefer the attending to discuss code status, nearly 70% of respondents disagreed.

Of those residents who said they preferred to retain the code-status discussion, 93.4% said they thought it was part of their responsibility as a physician, and 65.8% said they thought they had sufficient training and knowledge to do it. A minority in this group (2.5%) said that they would be likely to disagree with the attending’s estimate of prognosis, and 4.9% said they thought the attending would not share his/her estimate honestly.

When the authors asked about the residents’ general satisfaction with discussion of code status, “we learned two things: one, the residents are significantly more satisfied with their own discussions than their attendings’ discussions; and two, there is a substantial minority that is dissatisfied with all discussions, and a small number who are actually very satisfied,” Dr. Einstein said.

In a linear regression analysis testing for hypothesized correlations, the investigators found that more-senior residents were more likely to share prognostic information and make recommendations (P = .002). Residents who expressed an interest in hematology/oncology or palliative care specialization were also more likely to offer prognostic information, but not to make a recommendation about code status.

More-senior year of training correlated negatively with satisfaction with both the resident’s own and the attending’s discussion of code status.

“We found substantial dissatisfaction with code-status discussions in general, and we hypothesize that this is due to an internal conflict. When a resident knows that an intervention may be more harmful than beneficial, but thinks that the patient should make their own decision alone, then one may experience substantial frustration, and this would increase as training goes on and one becomes more sure of the outcomes of interventions like CPR,” Dr. Einstein said.

Generation gap

Evoking a potential generation gap between old-school doctors and the up-and-coming young physicians who by statute work fewer hours than their mentors had to, “I’m struck that [residents] don’t trust the attendings. When I was a resident, you didn’t do anything without asking the attending,” said Dr. Michael H. Levy, an invited discussant who is vice chair of medical oncology and director of the pain and palliative care program at Fox Chase Cancer Center, Philadelphia.

“I’m glad that the residents want to do it, but they have the same arrogance/ignorance that they don’t know how, so if we want them to do it, we have to train them,” he said.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. The study was supported in part by the Conquer Cancer Foundation. Dr. Einstein and Dr. Levy reported having no relevant disclosures.

BOSTON – Medical residents in the United States appear to understand that cardiopulmonary resuscitation or intubation is highly unlikely to benefit patients with advanced cancers at the end of life, but the majority of residents surveyed said that they do not discuss code-status options or potentially beneficial palliative care with their dying patients.

“This was primarily due to residents’ perceptions of patient autonomy: Residents wanted patients to make their own decisions, without any influence from the doctor, which misses the concept of informed decision making. These incomplete discussions can cause at minimum improper documentation of patients’ wishes, and at most psychological harm, damage to the physician-patient relationship, and the potential for unwanted attempts at resuscitation,” said Dr. David J. Einstein, a resident at Beth Israel Deaconess Medical Center and Tufts Medical Center, both in Boston.

Despite their reluctance to have the discussion, however, the majority of residents said they preferred to discuss code status with patients themselves rather than hand it off to the attending physician, primarily out of a sense that it is their responsibility as physicians. Yet these physicians in training did not seem to feel that they were also responsible for providing guidance to patients, Dr. Einstein said at the Palliative Care in Oncology Symposium.

“We felt that this represented an unmet need in training and practice. Residents and attendings should be providing guidance on all medical interventions, including CPR, and if they aren’t sure what to recommend, then they themselves should be seeking guidance from other experts, before asking a patient to falsely choose between an intervention and death,” he said.

The first discussion of code status – do not resuscitate (DNR) or do not intubate (DNI) – may occur in the hospital, and is often left to a resident physician. Ideally, the physician and patient should discuss the patient’s prognosis, goals for care, evaluation of CPR as a means of meeting those goals, and a recommendation. But many residents lack training in the end-of-life discussion, which can have a significant impact on the quality of the patients’ remaining weeks or months of life.

Nationwide survey

Dr. Einstein and his colleagues conducted a nationwide survey to measure the likelihood that residents would discuss prognostic information and offer recommendations to patients with limited life expectancy. They also sought to determine why residents might be reluctant to provide discussion, and to evaluate their satisfaction with code-status discussions that both they and their attending physicians have conducted.

The survey presented respondents with a hypothetical case of a patient with stage IV adenocarcinoma of the lung metastatic to the brain. The patient, who has disease progression despite receiving first- and second-line therapy, presents to the emergency department with dyspnea and is slightly hypoxemic, but is not in distress. The patient has not previously established a code-status preference.

The investigators contacted 387 residency program directors by mail, 19 of whom agreed to participate and responded. They sent surveys to a total of 1,627 residents, 358 of which were completed and included.

The investigators found that slightly less than half of the respondents said they would share information with the patient about his/her prognosis and the relative benefit of CPR, and more than two-thirds said they would be unlikely to offer a specific recommendation.

“So even in the situation with a clearly declining patient, residents were as likely as not to provide the information needed to make an informed decision, and were far less likely to provide guidance on this decision,” Dr. Einstein said.

Asked the reason for their decisions, 69% of the residents who would not offer a recommendation said that the patient should make his/her own decision without any influence, and 26.5% said that the attending would not want them to offer a recommendation. Nonetheless, only 1.3% of this group said they believed that CPR would offer the patient a reasonable chance of resuscitation.

The majority of respondents who would offer a recommendation (93.5%) said they would recommend DNR and DNI.

Code-status talk a ‘responsibility’

When they were asked whether they would prefer the attending to discuss code status, nearly 70% of respondents disagreed.

Of those residents who said they preferred to retain the code-status discussion, 93.4% said they thought it was part of their responsibility as a physician, and 65.8% said they thought they had sufficient training and knowledge to do it. A minority in this group (2.5%) said that they would be likely to disagree with the attending’s estimate of prognosis, and 4.9% said they thought the attending would not share his/her estimate honestly.

When the authors asked about the residents’ general satisfaction with discussion of code status, “we learned two things: one, the residents are significantly more satisfied with their own discussions than their attendings’ discussions; and two, there is a substantial minority that is dissatisfied with all discussions, and a small number who are actually very satisfied,” Dr. Einstein said.

In a linear regression analysis testing for hypothesized correlations, the investigators found that more-senior residents were more likely to share prognostic information and make recommendations (P = .002). Residents who expressed an interest in hematology/oncology or palliative care specialization were also more likely to offer prognostic information, but not to make a recommendation about code status.

More-senior year of training correlated negatively with satisfaction with both the resident’s own and the attending’s discussion of code status.

“We found substantial dissatisfaction with code-status discussions in general, and we hypothesize that this is due to an internal conflict. When a resident knows that an intervention may be more harmful than beneficial, but thinks that the patient should make their own decision alone, then one may experience substantial frustration, and this would increase as training goes on and one becomes more sure of the outcomes of interventions like CPR,” Dr. Einstein said.

Generation gap

Evoking a potential generation gap between old-school doctors and the up-and-coming young physicians who by statute work fewer hours than their mentors had to, “I’m struck that [residents] don’t trust the attendings. When I was a resident, you didn’t do anything without asking the attending,” said Dr. Michael H. Levy, an invited discussant who is vice chair of medical oncology and director of the pain and palliative care program at Fox Chase Cancer Center, Philadelphia.

“I’m glad that the residents want to do it, but they have the same arrogance/ignorance that they don’t know how, so if we want them to do it, we have to train them,” he said.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC. The study was supported in part by the Conquer Cancer Foundation. Dr. Einstein and Dr. Levy reported having no relevant disclosures.

BOSTON – When a palliative care oncologist partners with a medical oncologist on everyday rounds and in everyday practice on an inpatient floor, both patients and the clinicians who provide their care benefit from the arrangement, an oncologist reports.

At Duke University Medical Center in Durham, N.C., where palliative care is integrated with medical oncology on an inpatient oncology ward, the “co-rounding” model is associated with improvements in quality outcomes, improved nursing and physician satisfaction, and increased collaboration and communication, said Dr. Richard F. Riedel of the medical center.

In a study comparing the periods before and after implementation of the co-rounding model, lengths of stay and 7- and 30-day readmission rates were significantly shorter with co-rounding.

“I’d like to think that decreased resource utilization through decreased ICU transfer rates and decreased readmissions will result in a cost savings that would certainly justify putting a second provider up on an inpatient ward,” he said at the Palliative Care in Oncology Symposium.

The co-rounding model was introduced at Duke in 2011. Under this system, a medical oncologist and palliative care oncologist meet three times daily with house staff, fellows, and other team members to discuss the care of all patients on the unit. They decide which physician will oversee care of which patient. Patients who have high symptom burdens, for example, might be assigned to the palliative care physician. The physicians and staff go on rounds together with support staff, including internal medicine house staff, physician assistants, and pharmacists, allowing both formal and “curbside” consultations about how best to manage each patient.

“Critical to the success of this model is open communication and collaboration. We have three points where we meet throughout the day, and we emphasize to our colleagues that we are one team – we do not work in silos,” Dr. Riedel said.

Before and after

To see whether the co-rounding model was really, as they thought, a better way of doing business, Dr. Riedel and his colleagues conducted a retrospective cohort analysis of all patients admitted to the solid tumor inpatient service before the intervention – 731 patients admitted from September 2008 through June 2010 – compared with 783 admitted from September 2011 through June 2012, in the first year of co-rounding.

They found that co-rounding was associated with a significantly lower mean length of stay (4.51 days pre-intervention to 4.16 post, P =.02), and in both 7-day and 30-day readmission rates (12.1% vs. 9.3%, P <.0001, and 32.1% vs 28.3%, P = .048, respectively).

Although there were numerically fewer ICU transfers post intervention, this difference was not significant. Similarly, there was a trend, albeit nonsignificant, toward more hospice referrals under co-rounding.

When the researchers surveyed registered nurses who worked in the unit during both periods, they found that most agreed that adding a palliative care specialist improved quality of care, allowed for earlier goals-of-care discussions with patients, improved the involvement of nurses in care planning, reduced stresses on the staff, and improved symptom management.

Importantly, the improvements came without making rounds take longer or detracting from any appropriate focus on oncologic care, the authors found.

Medical oncology faculty who had rounded at least 2 weeks under the new regimen were surveyed, and they uniformly reported that the palliative care providers added a valuable skill set, that palliative care was a necessary component of cancer care, and that the rounding experience was more enjoyable. They also agreed that palliative care is different from hospice care, and said they felt that the discussion of hospice for those patients with incurable disease did not come too soon in the course of care,

“Importantly, the majority of physicians felt that they learned some new ways to manage symptoms, and I can tell you that I certainly have. I’m a medical oncologist, I’m not a palliative-care trained physician,” Dr. Riedel said.

He acknowledged that the study was limited by its retrospective design and the lack of a patient satisfaction component. Also, the intervention occurred at a single large academic medical center, and involved a smaller physician-to-patient ratio that could have confounded results.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

BOSTON – When a palliative care oncologist partners with a medical oncologist on everyday rounds and in everyday practice on an inpatient floor, both patients and the clinicians who provide their care benefit from the arrangement, an oncologist reports.

At Duke University Medical Center in Durham, N.C., where palliative care is integrated with medical oncology on an inpatient oncology ward, the “co-rounding” model is associated with improvements in quality outcomes, improved nursing and physician satisfaction, and increased collaboration and communication, said Dr. Richard F. Riedel of the medical center.

In a study comparing the periods before and after implementation of the co-rounding model, lengths of stay and 7- and 30-day readmission rates were significantly shorter with co-rounding.

“I’d like to think that decreased resource utilization through decreased ICU transfer rates and decreased readmissions will result in a cost savings that would certainly justify putting a second provider up on an inpatient ward,” he said at the Palliative Care in Oncology Symposium.

The co-rounding model was introduced at Duke in 2011. Under this system, a medical oncologist and palliative care oncologist meet three times daily with house staff, fellows, and other team members to discuss the care of all patients on the unit. They decide which physician will oversee care of which patient. Patients who have high symptom burdens, for example, might be assigned to the palliative care physician. The physicians and staff go on rounds together with support staff, including internal medicine house staff, physician assistants, and pharmacists, allowing both formal and “curbside” consultations about how best to manage each patient.

“Critical to the success of this model is open communication and collaboration. We have three points where we meet throughout the day, and we emphasize to our colleagues that we are one team – we do not work in silos,” Dr. Riedel said.

Before and after

To see whether the co-rounding model was really, as they thought, a better way of doing business, Dr. Riedel and his colleagues conducted a retrospective cohort analysis of all patients admitted to the solid tumor inpatient service before the intervention – 731 patients admitted from September 2008 through June 2010 – compared with 783 admitted from September 2011 through June 2012, in the first year of co-rounding.

They found that co-rounding was associated with a significantly lower mean length of stay (4.51 days pre-intervention to 4.16 post, P =.02), and in both 7-day and 30-day readmission rates (12.1% vs. 9.3%, P <.0001, and 32.1% vs 28.3%, P = .048, respectively).

Although there were numerically fewer ICU transfers post intervention, this difference was not significant. Similarly, there was a trend, albeit nonsignificant, toward more hospice referrals under co-rounding.

When the researchers surveyed registered nurses who worked in the unit during both periods, they found that most agreed that adding a palliative care specialist improved quality of care, allowed for earlier goals-of-care discussions with patients, improved the involvement of nurses in care planning, reduced stresses on the staff, and improved symptom management.

Importantly, the improvements came without making rounds take longer or detracting from any appropriate focus on oncologic care, the authors found.

Medical oncology faculty who had rounded at least 2 weeks under the new regimen were surveyed, and they uniformly reported that the palliative care providers added a valuable skill set, that palliative care was a necessary component of cancer care, and that the rounding experience was more enjoyable. They also agreed that palliative care is different from hospice care, and said they felt that the discussion of hospice for those patients with incurable disease did not come too soon in the course of care,

“Importantly, the majority of physicians felt that they learned some new ways to manage symptoms, and I can tell you that I certainly have. I’m a medical oncologist, I’m not a palliative-care trained physician,” Dr. Riedel said.

He acknowledged that the study was limited by its retrospective design and the lack of a patient satisfaction component. Also, the intervention occurred at a single large academic medical center, and involved a smaller physician-to-patient ratio that could have confounded results.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

BOSTON – When a palliative care oncologist partners with a medical oncologist on everyday rounds and in everyday practice on an inpatient floor, both patients and the clinicians who provide their care benefit from the arrangement, an oncologist reports.

At Duke University Medical Center in Durham, N.C., where palliative care is integrated with medical oncology on an inpatient oncology ward, the “co-rounding” model is associated with improvements in quality outcomes, improved nursing and physician satisfaction, and increased collaboration and communication, said Dr. Richard F. Riedel of the medical center.

In a study comparing the periods before and after implementation of the co-rounding model, lengths of stay and 7- and 30-day readmission rates were significantly shorter with co-rounding.

“I’d like to think that decreased resource utilization through decreased ICU transfer rates and decreased readmissions will result in a cost savings that would certainly justify putting a second provider up on an inpatient ward,” he said at the Palliative Care in Oncology Symposium.

The co-rounding model was introduced at Duke in 2011. Under this system, a medical oncologist and palliative care oncologist meet three times daily with house staff, fellows, and other team members to discuss the care of all patients on the unit. They decide which physician will oversee care of which patient. Patients who have high symptom burdens, for example, might be assigned to the palliative care physician. The physicians and staff go on rounds together with support staff, including internal medicine house staff, physician assistants, and pharmacists, allowing both formal and “curbside” consultations about how best to manage each patient.

“Critical to the success of this model is open communication and collaboration. We have three points where we meet throughout the day, and we emphasize to our colleagues that we are one team – we do not work in silos,” Dr. Riedel said.

Before and after

To see whether the co-rounding model was really, as they thought, a better way of doing business, Dr. Riedel and his colleagues conducted a retrospective cohort analysis of all patients admitted to the solid tumor inpatient service before the intervention – 731 patients admitted from September 2008 through June 2010 – compared with 783 admitted from September 2011 through June 2012, in the first year of co-rounding.

They found that co-rounding was associated with a significantly lower mean length of stay (4.51 days pre-intervention to 4.16 post, P =.02), and in both 7-day and 30-day readmission rates (12.1% vs. 9.3%, P <.0001, and 32.1% vs 28.3%, P = .048, respectively).

Although there were numerically fewer ICU transfers post intervention, this difference was not significant. Similarly, there was a trend, albeit nonsignificant, toward more hospice referrals under co-rounding.

When the researchers surveyed registered nurses who worked in the unit during both periods, they found that most agreed that adding a palliative care specialist improved quality of care, allowed for earlier goals-of-care discussions with patients, improved the involvement of nurses in care planning, reduced stresses on the staff, and improved symptom management.

Importantly, the improvements came without making rounds take longer or detracting from any appropriate focus on oncologic care, the authors found.

Medical oncology faculty who had rounded at least 2 weeks under the new regimen were surveyed, and they uniformly reported that the palliative care providers added a valuable skill set, that palliative care was a necessary component of cancer care, and that the rounding experience was more enjoyable. They also agreed that palliative care is different from hospice care, and said they felt that the discussion of hospice for those patients with incurable disease did not come too soon in the course of care,

“Importantly, the majority of physicians felt that they learned some new ways to manage symptoms, and I can tell you that I certainly have. I’m a medical oncologist, I’m not a palliative-care trained physician,” Dr. Riedel said.

He acknowledged that the study was limited by its retrospective design and the lack of a patient satisfaction component. Also, the intervention occurred at a single large academic medical center, and involved a smaller physician-to-patient ratio that could have confounded results.

The symposium was cosponsored by AAHPM, ASCO, ASTRO, and MASCC.

BOSTON – Further parsing of data from the SCALE clinical trials reinforces the finding that an investigational dose of liraglutide, combined with diet and exercise, is linked with more weight loss in obese diabetic and nondiabetic adults than diet and exercise alone, albeit with significant GI adverse effects.

Among patients who completed the 56-week SCALE Obesity and Prediabetes trial, obese and prediabetic adults treated with an investigational 3-mg injectable daily dose of liraglutide plus calorie restriction and exercise lost a mean of 9.2% of their body weight, compared with 3.5% for patients who injected themselves with placebo and also dieted and exercised.

“Liraglutide 3 mg, in obese patients with prediabetes and without prediabetes, gave significantly more weight loss than in the placebo group, and it was independent of whether or not patients had prediabetes, or their body mass index,” Dr. Frank Greenway of the Pennington Biomedical Research Center in Baton Rouge, La., said at Obesity Week 2014, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Patients with a baseline BMI of up to 29.9 kg/m² lost an average of 7.5% of body weight, those with a BMI of 30-34.9 lost 8.3%, those with a BMI of 35-39.9% dropped 9.3% on average, and those with BMIs of 40 or over shed 7.4%. In each category, the difference between the liraglutide and placebo groups was significant (P < .0001).

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue approved in the United States as a 1.2-mg and 1.8-mg daily subcutaneous injection as an adjunct to diet and exercise in patients with type 2 diabetes. It is not recommended as first-line therapy for patients with diabetes that is not adequately controlled with diet and exercise. On the basis of the results of the SCALE trials and others, advisers to the Food and Drug Administration in September recommended that the 3-mg dose be approved for weight management in adults. At press time, no decision on the application by the manufacturer, Novo Nordisk, had been made by the FDA.

The SCALE trial enrolled 3,731 patients and randomized them on a 2:1 basis to liraglutide (2,487) or placebo (1,244).

GI adverse events common

The most common adverse event with liraglutide over the course of the study was nausea, which occurred in 40% of patients who injected the drug, compared with 15% of patients who injected a placebo. Diarrhea occurred in 21% and 9%., respectively, and vomiting occurred in 16% and 4%.

Despite these adverse events, which tended to peak by the 6th to 8th week of the study, more patients in the placebo group dropped out of the study (28.1% vs. 35.6%), said Dr. Ken Fujioka of the department of nutrition and metabolic research at the Scripps Clinic in La Jolla, Calif.

“This is a high rate of nausea,” Dr. Fujioka said. He noted that the trial protocol required an upward dose titration that could not be reversed without causing the patient to exit the study, which could partially explain the high rate of gastrointestinal distress seen with the drug.

Dr. Fujioka reported health-related quality of life data from the trial, based on scores in the Short Form–36 (SF-36) and Impact of Weight on Quality of Life–Lite (IWQoL-Lite) questionnaires, which showed better, albeit modest, gains over baselines in patients on liraglutide compared with placebo.

Liraglutide in diabetes patients

Dr. Robert F. Kushner of Northwestern University, Chicago, reported results from a separate trial from the SCALE clinical trial series, SCALE-Diabetes, looking at health-related quality of life in 846 overweight or obese patients with type 2 diabetes treated with liraglutide at the investigational 3-mg dose, the approved 1.8-mg dose, or placebo. All patients also engaged in calorie restriction and exercise.

At week 56, the mean body weight percentage lost from baseline was 5.9% in the 3-mg group, 4.6% in the 1.8 mg group, and 2% in the placebo group.

Compared with placebo, there was a significantly better mean total improvement in the IWQoL-Lite score with the 3-mg dose but not with the 1.8-mg dose. Gastrointestinal adverse events also were common in this trial, with nausea occurring in 33% on the 3-mg dose, 31% on the 1.8-mg dose, and 14% of patients on placebo. Diarrhea occurred in 26%, 18%, and 13%, respectively, and constipation in 16%, 10%, and 6%.

“The nausea that is seen in this trial primarily occurs from the first 12-16 weeks and then settles down, and there is not that much difference thereafter,” Dr. Kushner said.

Too expensive?

An obesity researcher who was not involved in the study noted that liraglutide is not yet reimbursed for weight loss, and has an adverse event profile that may discourage some patients from remaining on the drug.

“I think that for those people who can tolerate the medication and who can afford it, it’s better than placebo. If you can have access to medication it’s great, but a lot of people are not able to stick to it for any duration of time, and that’s the downside of it. If you don’t stick to it, the weight comes back,” Dr. Ranjan Sudan, a surgeon at Duke University, Durham, N.C., and chair of the ASMBS Research Committee, said in an interview.

“If this medication, for instance, could show that down the road it prevented or prolonged the onset of diabetes, that would be a whole different thing, and there may be some justification for its use. But for the moment, being primarily for weight loss purposes and not to treat comorbidities makes it a little bit of a hard sell,” he said.

If approved, liraglutide 3 mg will be marketed as Saxenda. Liraglutide 1.8 mg was approved in 2010 and is marketed as Victoza.

The studies were supported by Novo Nordisk. Dr. Greenway and Dr. Kushner disclosed serving on the company’s advisory board. Dr. Fujioka disclosed receiving research support and consulting with the company.

BOSTON – Further parsing of data from the SCALE clinical trials reinforces the finding that an investigational dose of liraglutide, combined with diet and exercise, is linked with more weight loss in obese diabetic and nondiabetic adults than diet and exercise alone, albeit with significant GI adverse effects.

Among patients who completed the 56-week SCALE Obesity and Prediabetes trial, obese and prediabetic adults treated with an investigational 3-mg injectable daily dose of liraglutide plus calorie restriction and exercise lost a mean of 9.2% of their body weight, compared with 3.5% for patients who injected themselves with placebo and also dieted and exercised.

“Liraglutide 3 mg, in obese patients with prediabetes and without prediabetes, gave significantly more weight loss than in the placebo group, and it was independent of whether or not patients had prediabetes, or their body mass index,” Dr. Frank Greenway of the Pennington Biomedical Research Center in Baton Rouge, La., said at Obesity Week 2014, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Patients with a baseline BMI of up to 29.9 kg/m² lost an average of 7.5% of body weight, those with a BMI of 30-34.9 lost 8.3%, those with a BMI of 35-39.9% dropped 9.3% on average, and those with BMIs of 40 or over shed 7.4%. In each category, the difference between the liraglutide and placebo groups was significant (P < .0001).

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue approved in the United States as a 1.2-mg and 1.8-mg daily subcutaneous injection as an adjunct to diet and exercise in patients with type 2 diabetes. It is not recommended as first-line therapy for patients with diabetes that is not adequately controlled with diet and exercise. On the basis of the results of the SCALE trials and others, advisers to the Food and Drug Administration in September recommended that the 3-mg dose be approved for weight management in adults. At press time, no decision on the application by the manufacturer, Novo Nordisk, had been made by the FDA.

The SCALE trial enrolled 3,731 patients and randomized them on a 2:1 basis to liraglutide (2,487) or placebo (1,244).

GI adverse events common

The most common adverse event with liraglutide over the course of the study was nausea, which occurred in 40% of patients who injected the drug, compared with 15% of patients who injected a placebo. Diarrhea occurred in 21% and 9%., respectively, and vomiting occurred in 16% and 4%.

Despite these adverse events, which tended to peak by the 6th to 8th week of the study, more patients in the placebo group dropped out of the study (28.1% vs. 35.6%), said Dr. Ken Fujioka of the department of nutrition and metabolic research at the Scripps Clinic in La Jolla, Calif.

“This is a high rate of nausea,” Dr. Fujioka said. He noted that the trial protocol required an upward dose titration that could not be reversed without causing the patient to exit the study, which could partially explain the high rate of gastrointestinal distress seen with the drug.

Dr. Fujioka reported health-related quality of life data from the trial, based on scores in the Short Form–36 (SF-36) and Impact of Weight on Quality of Life–Lite (IWQoL-Lite) questionnaires, which showed better, albeit modest, gains over baselines in patients on liraglutide compared with placebo.

Liraglutide in diabetes patients

Dr. Robert F. Kushner of Northwestern University, Chicago, reported results from a separate trial from the SCALE clinical trial series, SCALE-Diabetes, looking at health-related quality of life in 846 overweight or obese patients with type 2 diabetes treated with liraglutide at the investigational 3-mg dose, the approved 1.8-mg dose, or placebo. All patients also engaged in calorie restriction and exercise.

At week 56, the mean body weight percentage lost from baseline was 5.9% in the 3-mg group, 4.6% in the 1.8 mg group, and 2% in the placebo group.

Compared with placebo, there was a significantly better mean total improvement in the IWQoL-Lite score with the 3-mg dose but not with the 1.8-mg dose. Gastrointestinal adverse events also were common in this trial, with nausea occurring in 33% on the 3-mg dose, 31% on the 1.8-mg dose, and 14% of patients on placebo. Diarrhea occurred in 26%, 18%, and 13%, respectively, and constipation in 16%, 10%, and 6%.

“The nausea that is seen in this trial primarily occurs from the first 12-16 weeks and then settles down, and there is not that much difference thereafter,” Dr. Kushner said.

Too expensive?

An obesity researcher who was not involved in the study noted that liraglutide is not yet reimbursed for weight loss, and has an adverse event profile that may discourage some patients from remaining on the drug.

“I think that for those people who can tolerate the medication and who can afford it, it’s better than placebo. If you can have access to medication it’s great, but a lot of people are not able to stick to it for any duration of time, and that’s the downside of it. If you don’t stick to it, the weight comes back,” Dr. Ranjan Sudan, a surgeon at Duke University, Durham, N.C., and chair of the ASMBS Research Committee, said in an interview.

“If this medication, for instance, could show that down the road it prevented or prolonged the onset of diabetes, that would be a whole different thing, and there may be some justification for its use. But for the moment, being primarily for weight loss purposes and not to treat comorbidities makes it a little bit of a hard sell,” he said.

If approved, liraglutide 3 mg will be marketed as Saxenda. Liraglutide 1.8 mg was approved in 2010 and is marketed as Victoza.

The studies were supported by Novo Nordisk. Dr. Greenway and Dr. Kushner disclosed serving on the company’s advisory board. Dr. Fujioka disclosed receiving research support and consulting with the company.

BOSTON – Further parsing of data from the SCALE clinical trials reinforces the finding that an investigational dose of liraglutide, combined with diet and exercise, is linked with more weight loss in obese diabetic and nondiabetic adults than diet and exercise alone, albeit with significant GI adverse effects.

Among patients who completed the 56-week SCALE Obesity and Prediabetes trial, obese and prediabetic adults treated with an investigational 3-mg injectable daily dose of liraglutide plus calorie restriction and exercise lost a mean of 9.2% of their body weight, compared with 3.5% for patients who injected themselves with placebo and also dieted and exercised.

“Liraglutide 3 mg, in obese patients with prediabetes and without prediabetes, gave significantly more weight loss than in the placebo group, and it was independent of whether or not patients had prediabetes, or their body mass index,” Dr. Frank Greenway of the Pennington Biomedical Research Center in Baton Rouge, La., said at Obesity Week 2014, presented by the Obesity Society and the American Society for Metabolic and Bariatric Surgery.

Patients with a baseline BMI of up to 29.9 kg/m² lost an average of 7.5% of body weight, those with a BMI of 30-34.9 lost 8.3%, those with a BMI of 35-39.9% dropped 9.3% on average, and those with BMIs of 40 or over shed 7.4%. In each category, the difference between the liraglutide and placebo groups was significant (P < .0001).

Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue approved in the United States as a 1.2-mg and 1.8-mg daily subcutaneous injection as an adjunct to diet and exercise in patients with type 2 diabetes. It is not recommended as first-line therapy for patients with diabetes that is not adequately controlled with diet and exercise. On the basis of the results of the SCALE trials and others, advisers to the Food and Drug Administration in September recommended that the 3-mg dose be approved for weight management in adults. At press time, no decision on the application by the manufacturer, Novo Nordisk, had been made by the FDA.

The SCALE trial enrolled 3,731 patients and randomized them on a 2:1 basis to liraglutide (2,487) or placebo (1,244).

GI adverse events common

The most common adverse event with liraglutide over the course of the study was nausea, which occurred in 40% of patients who injected the drug, compared with 15% of patients who injected a placebo. Diarrhea occurred in 21% and 9%., respectively, and vomiting occurred in 16% and 4%.

Despite these adverse events, which tended to peak by the 6th to 8th week of the study, more patients in the placebo group dropped out of the study (28.1% vs. 35.6%), said Dr. Ken Fujioka of the department of nutrition and metabolic research at the Scripps Clinic in La Jolla, Calif.

“This is a high rate of nausea,” Dr. Fujioka said. He noted that the trial protocol required an upward dose titration that could not be reversed without causing the patient to exit the study, which could partially explain the high rate of gastrointestinal distress seen with the drug.

Dr. Fujioka reported health-related quality of life data from the trial, based on scores in the Short Form–36 (SF-36) and Impact of Weight on Quality of Life–Lite (IWQoL-Lite) questionnaires, which showed better, albeit modest, gains over baselines in patients on liraglutide compared with placebo.

Liraglutide in diabetes patients

Dr. Robert F. Kushner of Northwestern University, Chicago, reported results from a separate trial from the SCALE clinical trial series, SCALE-Diabetes, looking at health-related quality of life in 846 overweight or obese patients with type 2 diabetes treated with liraglutide at the investigational 3-mg dose, the approved 1.8-mg dose, or placebo. All patients also engaged in calorie restriction and exercise.

At week 56, the mean body weight percentage lost from baseline was 5.9% in the 3-mg group, 4.6% in the 1.8 mg group, and 2% in the placebo group.

Compared with placebo, there was a significantly better mean total improvement in the IWQoL-Lite score with the 3-mg dose but not with the 1.8-mg dose. Gastrointestinal adverse events also were common in this trial, with nausea occurring in 33% on the 3-mg dose, 31% on the 1.8-mg dose, and 14% of patients on placebo. Diarrhea occurred in 26%, 18%, and 13%, respectively, and constipation in 16%, 10%, and 6%.

“The nausea that is seen in this trial primarily occurs from the first 12-16 weeks and then settles down, and there is not that much difference thereafter,” Dr. Kushner said.

Too expensive?

An obesity researcher who was not involved in the study noted that liraglutide is not yet reimbursed for weight loss, and has an adverse event profile that may discourage some patients from remaining on the drug.

“I think that for those people who can tolerate the medication and who can afford it, it’s better than placebo. If you can have access to medication it’s great, but a lot of people are not able to stick to it for any duration of time, and that’s the downside of it. If you don’t stick to it, the weight comes back,” Dr. Ranjan Sudan, a surgeon at Duke University, Durham, N.C., and chair of the ASMBS Research Committee, said in an interview.

“If this medication, for instance, could show that down the road it prevented or prolonged the onset of diabetes, that would be a whole different thing, and there may be some justification for its use. But for the moment, being primarily for weight loss purposes and not to treat comorbidities makes it a little bit of a hard sell,” he said.

If approved, liraglutide 3 mg will be marketed as Saxenda. Liraglutide 1.8 mg was approved in 2010 and is marketed as Victoza.

The studies were supported by Novo Nordisk. Dr. Greenway and Dr. Kushner disclosed serving on the company’s advisory board. Dr. Fujioka disclosed receiving research support and consulting with the company.