Diana Mahoney

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, Dr. Michelle A. Petri reported at the annual European Congress of Rheumatology. Belimumab inhibits B-lymphocyte stimulator. Among the "unanswered questions" about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug’s safety over time, said Dr. Petri, director of the lupus center at Johns Hopkins University, Baltimore.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10 mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA ) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group(BILAG) 1A/2B flares, the SLE responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. "Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1," she said.

Specifically, the SRI rate increased from 46% at year 1 to 55%-61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. "Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important," she explained.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Additionally, concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, compared with baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, "especially in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement," Dr. Petri said.

The findings of this study are limited by the potential for self-selection bias, in that patients not responding positively to the belimumab may have dropped out during the course of the study, while those benefiting from the drug would be more likely to continue treatment, Dr. Petri said. Even so, the safety and tolerability data suggest that, in "the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy."

Yet to be addressed "meaningfully" in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug’s effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, Dr. Michelle A. Petri reported at the annual European Congress of Rheumatology. Belimumab inhibits B-lymphocyte stimulator. Among the "unanswered questions" about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug’s safety over time, said Dr. Petri, director of the lupus center at Johns Hopkins University, Baltimore.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10 mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA ) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group(BILAG) 1A/2B flares, the SLE responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. "Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1," she said.

Specifically, the SRI rate increased from 46% at year 1 to 55%-61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. "Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important," she explained.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Additionally, concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, compared with baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, "especially in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement," Dr. Petri said.

The findings of this study are limited by the potential for self-selection bias, in that patients not responding positively to the belimumab may have dropped out during the course of the study, while those benefiting from the drug would be more likely to continue treatment, Dr. Petri said. Even so, the safety and tolerability data suggest that, in "the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy."

Yet to be addressed "meaningfully" in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug’s effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, Dr. Michelle A. Petri reported at the annual European Congress of Rheumatology. Belimumab inhibits B-lymphocyte stimulator. Among the "unanswered questions" about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug’s safety over time, said Dr. Petri, director of the lupus center at Johns Hopkins University, Baltimore.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10 mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA ) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group(BILAG) 1A/2B flares, the SLE responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. "Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1," she said.

Specifically, the SRI rate increased from 46% at year 1 to 55%-61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. "Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important," she explained.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Additionally, concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, compared with baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, "especially in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement," Dr. Petri said.

The findings of this study are limited by the potential for self-selection bias, in that patients not responding positively to the belimumab may have dropped out during the course of the study, while those benefiting from the drug would be more likely to continue treatment, Dr. Petri said. Even so, the safety and tolerability data suggest that, in "the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy."

Yet to be addressed "meaningfully" in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug’s effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, Dr. Michelle A. Petri reported at the annual European Congress of Rheumatology. Belimumab inhibits B-lymphocyte stimulator. Among the "unanswered questions" about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug’s safety over time, said Dr. Petri, director of the lupus center at Johns Hopkins University, Baltimore.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10 mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA ) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group(BILAG) 1A/2B flares, the SLE responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. "Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1," she said.

Specifically, the SRI rate increased from 46% at year 1 to 55%-61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. "Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important," she explained.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Additionally, concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, compared with baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, "especially in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement," Dr. Petri said.

The findings of this study are limited by the potential for self-selection bias, in that patients not responding positively to the belimumab may have dropped out during the course of the study, while those benefiting from the drug would be more likely to continue treatment, Dr. Petri said. Even so, the safety and tolerability data suggest that, in "the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy."

Yet to be addressed "meaningfully" in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug’s effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, Dr. Michelle A. Petri reported at the annual European Congress of Rheumatology. Belimumab inhibits B-lymphocyte stimulator. Among the "unanswered questions" about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug’s safety over time, said Dr. Petri, director of the lupus center at Johns Hopkins University, Baltimore.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10 mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA ) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group(BILAG) 1A/2B flares, the SLE responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. "Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1," she said.

Specifically, the SRI rate increased from 46% at year 1 to 55%-61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. "Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important," she explained.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Additionally, concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, compared with baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, "especially in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement," Dr. Petri said.

The findings of this study are limited by the potential for self-selection bias, in that patients not responding positively to the belimumab may have dropped out during the course of the study, while those benefiting from the drug would be more likely to continue treatment, Dr. Petri said. Even so, the safety and tolerability data suggest that, in "the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy."

Yet to be addressed "meaningfully" in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug’s effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, Dr. Michelle A. Petri reported at the annual European Congress of Rheumatology. Belimumab inhibits B-lymphocyte stimulator. Among the "unanswered questions" about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug’s safety over time, said Dr. Petri, director of the lupus center at Johns Hopkins University, Baltimore.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10 mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA ) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group(BILAG) 1A/2B flares, the SLE responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. "Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1," she said.

Specifically, the SRI rate increased from 46% at year 1 to 55%-61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. "Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important," she explained.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Additionally, concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, compared with baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, "especially in whom there is evidence that B-cells are driving disease activity, such as anti-DNA or low complement," Dr. Petri said.

The findings of this study are limited by the potential for self-selection bias, in that patients not responding positively to the belimumab may have dropped out during the course of the study, while those benefiting from the drug would be more likely to continue treatment, Dr. Petri said. Even so, the safety and tolerability data suggest that, in "the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy."

Yet to be addressed "meaningfully" in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug’s effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

MINNEAPOLIS – Maxillomandibular advancement may be a reasonable option for patients who have severe sleep apnea and are unable to tolerate continuous positive airway pressure therapy, according to a study by the Department of Veterans Affairs.

In maxillomandibular advancement (MMA), the upper and lower jaws are moved forward to optimize the airway and minimize soft-tissue blockages. Dr. Vincent Mysliwiec and his colleagues in the Critical Care Medicine and Sleep Medicine Service at Madigan Healthcare System, Joint Base Lewis-McChord in Tacoma, Wash., evaluated the outcomes of the surgery in an active-duty population.

"Obstructive sleep apnea is an increasingly common diagnosis in soldiers, and those soldiers with more severe cases are not deployable without going through an extensive waiver process," Dr. Mysliwiec said at the annual meeting of the Associated Professional Sleep Societies. "We wanted to assess whether [MMA] represents a surgical cure that can potentially remove the requirement for CPAP in these individuals and, in so doing, increase the number of soldiers who are fully deployable."

The researchers reviewed all of the MMA procedures performed for obstructive sleep apnea at their institution in 2006-2009 and identified 37 soldiers who had severe disease – defined as an apnea-hypopnea index (AHI) of more than 30 events/hr – and underwent the surgery as well as pre- and postoperative polysomnography. The primary study outcomes were comparisons of the pre- and postoperative AHI and minimum nocturnal oxyhemoglobin saturation. Surgical cure was defined as an AHI reduction of at least 50%, compared with preoperative AHI, and a postoperative AHI of less than 15.

The mean body mass index of the study cohort was 29 kg/m², and the mean preoperative AHI was 50.5, Dr. Mysliwiec reported. Following the procedure, "the mean postoperative [AHI] dropped significantly to 13.8," he said. "Twenty-two of the soldiers – nearly 60% of the group – reduced their [AHI] by at least half, which met the criteria for surgical cure." Further, he said, 16 of the soldiers had a postoperative AHI of less than 5, "meaning they had no residual disease at all following the procedure." One study patient did not experience a clinically significant reduction in AHI following the surgery. The mean minimum nocturnal oxyhemoglobin saturation increased postoperatively from 85% to 86%, a nonsignificant change (P = .21; standard deviation for both measures, 7%).

"Maxillomandibular advancement significantly reduced the severity of sleep apnea for our patients and improved the quality of their sleep," Dr. Mysliwiec said. "These findings could improve the standard of care for civilians and active-duty service members with severe obstructive sleep apnea who can’t tolerate CPAP or have failed other soft-tissue procedures."

Dr. Mysliwiec reported having no financial conflicts of interest.

MINNEAPOLIS – Maxillomandibular advancement may be a reasonable option for patients who have severe sleep apnea and are unable to tolerate continuous positive airway pressure therapy, according to a study by the Department of Veterans Affairs.

In maxillomandibular advancement (MMA), the upper and lower jaws are moved forward to optimize the airway and minimize soft-tissue blockages. Dr. Vincent Mysliwiec and his colleagues in the Critical Care Medicine and Sleep Medicine Service at Madigan Healthcare System, Joint Base Lewis-McChord in Tacoma, Wash., evaluated the outcomes of the surgery in an active-duty population.

"Obstructive sleep apnea is an increasingly common diagnosis in soldiers, and those soldiers with more severe cases are not deployable without going through an extensive waiver process," Dr. Mysliwiec said at the annual meeting of the Associated Professional Sleep Societies. "We wanted to assess whether [MMA] represents a surgical cure that can potentially remove the requirement for CPAP in these individuals and, in so doing, increase the number of soldiers who are fully deployable."

The researchers reviewed all of the MMA procedures performed for obstructive sleep apnea at their institution in 2006-2009 and identified 37 soldiers who had severe disease – defined as an apnea-hypopnea index (AHI) of more than 30 events/hr – and underwent the surgery as well as pre- and postoperative polysomnography. The primary study outcomes were comparisons of the pre- and postoperative AHI and minimum nocturnal oxyhemoglobin saturation. Surgical cure was defined as an AHI reduction of at least 50%, compared with preoperative AHI, and a postoperative AHI of less than 15.

The mean body mass index of the study cohort was 29 kg/m², and the mean preoperative AHI was 50.5, Dr. Mysliwiec reported. Following the procedure, "the mean postoperative [AHI] dropped significantly to 13.8," he said. "Twenty-two of the soldiers – nearly 60% of the group – reduced their [AHI] by at least half, which met the criteria for surgical cure." Further, he said, 16 of the soldiers had a postoperative AHI of less than 5, "meaning they had no residual disease at all following the procedure." One study patient did not experience a clinically significant reduction in AHI following the surgery. The mean minimum nocturnal oxyhemoglobin saturation increased postoperatively from 85% to 86%, a nonsignificant change (P = .21; standard deviation for both measures, 7%).

"Maxillomandibular advancement significantly reduced the severity of sleep apnea for our patients and improved the quality of their sleep," Dr. Mysliwiec said. "These findings could improve the standard of care for civilians and active-duty service members with severe obstructive sleep apnea who can’t tolerate CPAP or have failed other soft-tissue procedures."

Dr. Mysliwiec reported having no financial conflicts of interest.

MINNEAPOLIS – Maxillomandibular advancement may be a reasonable option for patients who have severe sleep apnea and are unable to tolerate continuous positive airway pressure therapy, according to a study by the Department of Veterans Affairs.

In maxillomandibular advancement (MMA), the upper and lower jaws are moved forward to optimize the airway and minimize soft-tissue blockages. Dr. Vincent Mysliwiec and his colleagues in the Critical Care Medicine and Sleep Medicine Service at Madigan Healthcare System, Joint Base Lewis-McChord in Tacoma, Wash., evaluated the outcomes of the surgery in an active-duty population.

"Obstructive sleep apnea is an increasingly common diagnosis in soldiers, and those soldiers with more severe cases are not deployable without going through an extensive waiver process," Dr. Mysliwiec said at the annual meeting of the Associated Professional Sleep Societies. "We wanted to assess whether [MMA] represents a surgical cure that can potentially remove the requirement for CPAP in these individuals and, in so doing, increase the number of soldiers who are fully deployable."

The researchers reviewed all of the MMA procedures performed for obstructive sleep apnea at their institution in 2006-2009 and identified 37 soldiers who had severe disease – defined as an apnea-hypopnea index (AHI) of more than 30 events/hr – and underwent the surgery as well as pre- and postoperative polysomnography. The primary study outcomes were comparisons of the pre- and postoperative AHI and minimum nocturnal oxyhemoglobin saturation. Surgical cure was defined as an AHI reduction of at least 50%, compared with preoperative AHI, and a postoperative AHI of less than 15.

The mean body mass index of the study cohort was 29 kg/m², and the mean preoperative AHI was 50.5, Dr. Mysliwiec reported. Following the procedure, "the mean postoperative [AHI] dropped significantly to 13.8," he said. "Twenty-two of the soldiers – nearly 60% of the group – reduced their [AHI] by at least half, which met the criteria for surgical cure." Further, he said, 16 of the soldiers had a postoperative AHI of less than 5, "meaning they had no residual disease at all following the procedure." One study patient did not experience a clinically significant reduction in AHI following the surgery. The mean minimum nocturnal oxyhemoglobin saturation increased postoperatively from 85% to 86%, a nonsignificant change (P = .21; standard deviation for both measures, 7%).

"Maxillomandibular advancement significantly reduced the severity of sleep apnea for our patients and improved the quality of their sleep," Dr. Mysliwiec said. "These findings could improve the standard of care for civilians and active-duty service members with severe obstructive sleep apnea who can’t tolerate CPAP or have failed other soft-tissue procedures."

Dr. Mysliwiec reported having no financial conflicts of interest.

MINNEAPOLIS – Maxillomandibular advancement may be a reasonable option for patients who have severe sleep apnea and are unable to tolerate continuous positive airway pressure therapy, according to a study by the Department of Veterans Affairs.

In maxillomandibular advancement (MMA), the upper and lower jaws are moved forward to optimize the airway and minimize soft-tissue blockages. Dr. Vincent Mysliwiec and his colleagues in the Critical Care Medicine and Sleep Medicine Service at Madigan Healthcare System, Joint Base Lewis-McChord in Tacoma, Wash., evaluated the outcomes of the surgery in an active-duty population.

"Obstructive sleep apnea is an increasingly common diagnosis in soldiers, and those soldiers with more severe cases are not deployable without going through an extensive waiver process," Dr. Mysliwiec said at the annual meeting of the Associated Professional Sleep Societies. "We wanted to assess whether [MMA] represents a surgical cure that can potentially remove the requirement for CPAP in these individuals and, in so doing, increase the number of soldiers who are fully deployable."

The researchers reviewed all of the MMA procedures performed for obstructive sleep apnea at their institution in 2006-2009 and identified 37 soldiers who had severe disease – defined as an apnea-hypopnea index (AHI) of more than 30 events/hr – and underwent the surgery as well as pre- and postoperative polysomnography. The primary study outcomes were comparisons of the pre- and postoperative AHI and minimum nocturnal oxyhemoglobin saturation. Surgical cure was defined as an AHI reduction of at least 50%, compared with preoperative AHI, and a postoperative AHI of less than 15.

The mean body mass index of the study cohort was 29 kg/m², and the mean preoperative AHI was 50.5, Dr. Mysliwiec reported. Following the procedure, "the mean postoperative [AHI] dropped significantly to 13.8," he said. "Twenty-two of the soldiers – nearly 60% of the group – reduced their [AHI] by at least half, which met the criteria for surgical cure." Further, he said, 16 of the soldiers had a postoperative AHI of less than 5, "meaning they had no residual disease at all following the procedure." One study patient did not experience a clinically significant reduction in AHI following the surgery. The mean minimum nocturnal oxyhemoglobin saturation increased postoperatively from 85% to 86%, a nonsignificant change (P = .21; standard deviation for both measures, 7%).

"Maxillomandibular advancement significantly reduced the severity of sleep apnea for our patients and improved the quality of their sleep," Dr. Mysliwiec said. "These findings could improve the standard of care for civilians and active-duty service members with severe obstructive sleep apnea who can’t tolerate CPAP or have failed other soft-tissue procedures."

Dr. Mysliwiec reported having no financial conflicts of interest.

MINNEAPOLIS – Maxillomandibular advancement may be a reasonable option for patients who have severe sleep apnea and are unable to tolerate continuous positive airway pressure therapy, according to a study by the Department of Veterans Affairs.

In maxillomandibular advancement (MMA), the upper and lower jaws are moved forward to optimize the airway and minimize soft-tissue blockages. Dr. Vincent Mysliwiec and his colleagues in the Critical Care Medicine and Sleep Medicine Service at Madigan Healthcare System, Joint Base Lewis-McChord in Tacoma, Wash., evaluated the outcomes of the surgery in an active-duty population.

"Obstructive sleep apnea is an increasingly common diagnosis in soldiers, and those soldiers with more severe cases are not deployable without going through an extensive waiver process," Dr. Mysliwiec said at the annual meeting of the Associated Professional Sleep Societies. "We wanted to assess whether [MMA] represents a surgical cure that can potentially remove the requirement for CPAP in these individuals and, in so doing, increase the number of soldiers who are fully deployable."

The researchers reviewed all of the MMA procedures performed for obstructive sleep apnea at their institution in 2006-2009 and identified 37 soldiers who had severe disease – defined as an apnea-hypopnea index (AHI) of more than 30 events/hr – and underwent the surgery as well as pre- and postoperative polysomnography. The primary study outcomes were comparisons of the pre- and postoperative AHI and minimum nocturnal oxyhemoglobin saturation. Surgical cure was defined as an AHI reduction of at least 50%, compared with preoperative AHI, and a postoperative AHI of less than 15.

The mean body mass index of the study cohort was 29 kg/m², and the mean preoperative AHI was 50.5, Dr. Mysliwiec reported. Following the procedure, "the mean postoperative [AHI] dropped significantly to 13.8," he said. "Twenty-two of the soldiers – nearly 60% of the group – reduced their [AHI] by at least half, which met the criteria for surgical cure." Further, he said, 16 of the soldiers had a postoperative AHI of less than 5, "meaning they had no residual disease at all following the procedure." One study patient did not experience a clinically significant reduction in AHI following the surgery. The mean minimum nocturnal oxyhemoglobin saturation increased postoperatively from 85% to 86%, a nonsignificant change (P = .21; standard deviation for both measures, 7%).

"Maxillomandibular advancement significantly reduced the severity of sleep apnea for our patients and improved the quality of their sleep," Dr. Mysliwiec said. "These findings could improve the standard of care for civilians and active-duty service members with severe obstructive sleep apnea who can’t tolerate CPAP or have failed other soft-tissue procedures."

Dr. Mysliwiec reported having no financial conflicts of interest.

MINNEAPOLIS – Maxillomandibular advancement may be a reasonable option for patients who have severe sleep apnea and are unable to tolerate continuous positive airway pressure therapy, according to a study by the Department of Veterans Affairs.

In maxillomandibular advancement (MMA), the upper and lower jaws are moved forward to optimize the airway and minimize soft-tissue blockages. Dr. Vincent Mysliwiec and his colleagues in the Critical Care Medicine and Sleep Medicine Service at Madigan Healthcare System, Joint Base Lewis-McChord in Tacoma, Wash., evaluated the outcomes of the surgery in an active-duty population.

"Obstructive sleep apnea is an increasingly common diagnosis in soldiers, and those soldiers with more severe cases are not deployable without going through an extensive waiver process," Dr. Mysliwiec said at the annual meeting of the Associated Professional Sleep Societies. "We wanted to assess whether [MMA] represents a surgical cure that can potentially remove the requirement for CPAP in these individuals and, in so doing, increase the number of soldiers who are fully deployable."

The researchers reviewed all of the MMA procedures performed for obstructive sleep apnea at their institution in 2006-2009 and identified 37 soldiers who had severe disease – defined as an apnea-hypopnea index (AHI) of more than 30 events/hr – and underwent the surgery as well as pre- and postoperative polysomnography. The primary study outcomes were comparisons of the pre- and postoperative AHI and minimum nocturnal oxyhemoglobin saturation. Surgical cure was defined as an AHI reduction of at least 50%, compared with preoperative AHI, and a postoperative AHI of less than 15.

The mean body mass index of the study cohort was 29 kg/m², and the mean preoperative AHI was 50.5, Dr. Mysliwiec reported. Following the procedure, "the mean postoperative [AHI] dropped significantly to 13.8," he said. "Twenty-two of the soldiers – nearly 60% of the group – reduced their [AHI] by at least half, which met the criteria for surgical cure." Further, he said, 16 of the soldiers had a postoperative AHI of less than 5, "meaning they had no residual disease at all following the procedure." One study patient did not experience a clinically significant reduction in AHI following the surgery. The mean minimum nocturnal oxyhemoglobin saturation increased postoperatively from 85% to 86%, a nonsignificant change (P = .21; standard deviation for both measures, 7%).

"Maxillomandibular advancement significantly reduced the severity of sleep apnea for our patients and improved the quality of their sleep," Dr. Mysliwiec said. "These findings could improve the standard of care for civilians and active-duty service members with severe obstructive sleep apnea who can’t tolerate CPAP or have failed other soft-tissue procedures."

Dr. Mysliwiec reported having no financial conflicts of interest.

MINNEAPOLIS – An automated analysis of tracheal breath sounds while awake was predictive of obstructive sleep apnea in a small study.

If validated in larger studies, the findings may streamline the obstructive sleep apnea (OSA) screening process, resulting in earlier diagnosis and treatment of severe cases, Zahra Moussavi, Ph.D., said at the annual meeting of the Associated Professional Sleep Societies. "The ability to predict the likelihood and severity of obstructive sleep apnea without performing overnight polysomnography is very appealing and would lead to significant reductions in health care costs, compared with full-night sleep assessments."

Obstructive sleep apnea (OSA) is highly prevalent in the general population, but only 30% of patients referred to a sleep lab for evaluation have severe OSA requiring treatment, said Dr. Moussavi, a professor in the department of electrical and computer engineering at the University of Manitoba, Winnipeg. With no fast, accurate, clinical or laboratory tools for predicting the severity of suspected OSA, full-night polysomnography is required to confirm the diagnosis and determine its severity. "Unfortunately, the demand [for full-night sleep studies] outweighs the available resources, resulting in appointment backlogs and long wait times, which can delay the initiation of potentially lifesaving care," she said.

Acoustic analysis has been used during sleep to evaluate the breathing and snoring patterns of suspected apnea patients. To examine wakeful breathing patterns associated with OSA, Dr. Moussavi and colleagues, recorded the tracheal breath sounds of 35 patients with varying severity of OSA and 17 age-matched controls.

"We recorded the tracheal breath sound in supine and upright positions during nose and mouth breathing," said Dr. Moussavi.

Spectral analysis of the respiratory signals indicated that variation in the average power of the tracheal breath sounds at different positions was a characteristic feature that discriminated the OSA and control groups.

Using the maximum relevancy/minimum redundancy method, the investigators reduced the number of sound features that were significantly different between the groups to two, "and unsupervised clustering of these showed an overall accuracy of 84%, with a sensitivity of 88% and a specificity of 80%," Dr. Moussavi reported.

"It is known that [OSA] patients have a smaller and more collapsible pharynx, which is compensated by increased dilator muscle activity during wakefulness. They tend to have more negative pharyngeal pressure, which can be detected via breathing sounds through the nose because of higher resistance," she said. Because breath sounds are directly related to pharyngeal pressure, "this method is sensitive to the severity of [OSA] even during wakefulness."

The study was supported by the National Sciences and Engineering Research Council of Canada and TRI Labs Winnipeg where Dr. Moussavi is an adjunct scientist.

MINNEAPOLIS – An automated analysis of tracheal breath sounds while awake was predictive of obstructive sleep apnea in a small study.

If validated in larger studies, the findings may streamline the obstructive sleep apnea (OSA) screening process, resulting in earlier diagnosis and treatment of severe cases, Zahra Moussavi, Ph.D., said at the annual meeting of the Associated Professional Sleep Societies. "The ability to predict the likelihood and severity of obstructive sleep apnea without performing overnight polysomnography is very appealing and would lead to significant reductions in health care costs, compared with full-night sleep assessments."

Obstructive sleep apnea (OSA) is highly prevalent in the general population, but only 30% of patients referred to a sleep lab for evaluation have severe OSA requiring treatment, said Dr. Moussavi, a professor in the department of electrical and computer engineering at the University of Manitoba, Winnipeg. With no fast, accurate, clinical or laboratory tools for predicting the severity of suspected OSA, full-night polysomnography is required to confirm the diagnosis and determine its severity. "Unfortunately, the demand [for full-night sleep studies] outweighs the available resources, resulting in appointment backlogs and long wait times, which can delay the initiation of potentially lifesaving care," she said.

Acoustic analysis has been used during sleep to evaluate the breathing and snoring patterns of suspected apnea patients. To examine wakeful breathing patterns associated with OSA, Dr. Moussavi and colleagues, recorded the tracheal breath sounds of 35 patients with varying severity of OSA and 17 age-matched controls.

"We recorded the tracheal breath sound in supine and upright positions during nose and mouth breathing," said Dr. Moussavi.

Spectral analysis of the respiratory signals indicated that variation in the average power of the tracheal breath sounds at different positions was a characteristic feature that discriminated the OSA and control groups.

Using the maximum relevancy/minimum redundancy method, the investigators reduced the number of sound features that were significantly different between the groups to two, "and unsupervised clustering of these showed an overall accuracy of 84%, with a sensitivity of 88% and a specificity of 80%," Dr. Moussavi reported.

"It is known that [OSA] patients have a smaller and more collapsible pharynx, which is compensated by increased dilator muscle activity during wakefulness. They tend to have more negative pharyngeal pressure, which can be detected via breathing sounds through the nose because of higher resistance," she said. Because breath sounds are directly related to pharyngeal pressure, "this method is sensitive to the severity of [OSA] even during wakefulness."

The study was supported by the National Sciences and Engineering Research Council of Canada and TRI Labs Winnipeg where Dr. Moussavi is an adjunct scientist.

MINNEAPOLIS – An automated analysis of tracheal breath sounds while awake was predictive of obstructive sleep apnea in a small study.

If validated in larger studies, the findings may streamline the obstructive sleep apnea (OSA) screening process, resulting in earlier diagnosis and treatment of severe cases, Zahra Moussavi, Ph.D., said at the annual meeting of the Associated Professional Sleep Societies. "The ability to predict the likelihood and severity of obstructive sleep apnea without performing overnight polysomnography is very appealing and would lead to significant reductions in health care costs, compared with full-night sleep assessments."

Obstructive sleep apnea (OSA) is highly prevalent in the general population, but only 30% of patients referred to a sleep lab for evaluation have severe OSA requiring treatment, said Dr. Moussavi, a professor in the department of electrical and computer engineering at the University of Manitoba, Winnipeg. With no fast, accurate, clinical or laboratory tools for predicting the severity of suspected OSA, full-night polysomnography is required to confirm the diagnosis and determine its severity. "Unfortunately, the demand [for full-night sleep studies] outweighs the available resources, resulting in appointment backlogs and long wait times, which can delay the initiation of potentially lifesaving care," she said.

Acoustic analysis has been used during sleep to evaluate the breathing and snoring patterns of suspected apnea patients. To examine wakeful breathing patterns associated with OSA, Dr. Moussavi and colleagues, recorded the tracheal breath sounds of 35 patients with varying severity of OSA and 17 age-matched controls.

"We recorded the tracheal breath sound in supine and upright positions during nose and mouth breathing," said Dr. Moussavi.

Spectral analysis of the respiratory signals indicated that variation in the average power of the tracheal breath sounds at different positions was a characteristic feature that discriminated the OSA and control groups.

Using the maximum relevancy/minimum redundancy method, the investigators reduced the number of sound features that were significantly different between the groups to two, "and unsupervised clustering of these showed an overall accuracy of 84%, with a sensitivity of 88% and a specificity of 80%," Dr. Moussavi reported.

"It is known that [OSA] patients have a smaller and more collapsible pharynx, which is compensated by increased dilator muscle activity during wakefulness. They tend to have more negative pharyngeal pressure, which can be detected via breathing sounds through the nose because of higher resistance," she said. Because breath sounds are directly related to pharyngeal pressure, "this method is sensitive to the severity of [OSA] even during wakefulness."

The study was supported by the National Sciences and Engineering Research Council of Canada and TRI Labs Winnipeg where Dr. Moussavi is an adjunct scientist.

MINNEAPOLIS – An automated analysis of tracheal breath sounds while awake was predictive of obstructive sleep apnea in a small study.

If validated in larger studies, the findings may streamline the obstructive sleep apnea (OSA) screening process, resulting in earlier diagnosis and treatment of severe cases, Zahra Moussavi, Ph.D., said at the annual meeting of the Associated Professional Sleep Societies. "The ability to predict the likelihood and severity of obstructive sleep apnea without performing overnight polysomnography is very appealing and would lead to significant reductions in health care costs, compared with full-night sleep assessments."

Obstructive sleep apnea (OSA) is highly prevalent in the general population, but only 30% of patients referred to a sleep lab for evaluation have severe OSA requiring treatment, said Dr. Moussavi, a professor in the department of electrical and computer engineering at the University of Manitoba, Winnipeg. With no fast, accurate, clinical or laboratory tools for predicting the severity of suspected OSA, full-night polysomnography is required to confirm the diagnosis and determine its severity. "Unfortunately, the demand [for full-night sleep studies] outweighs the available resources, resulting in appointment backlogs and long wait times, which can delay the initiation of potentially lifesaving care," she said.

Acoustic analysis has been used during sleep to evaluate the breathing and snoring patterns of suspected apnea patients. To examine wakeful breathing patterns associated with OSA, Dr. Moussavi and colleagues, recorded the tracheal breath sounds of 35 patients with varying severity of OSA and 17 age-matched controls.

"We recorded the tracheal breath sound in supine and upright positions during nose and mouth breathing," said Dr. Moussavi.

Spectral analysis of the respiratory signals indicated that variation in the average power of the tracheal breath sounds at different positions was a characteristic feature that discriminated the OSA and control groups.

Using the maximum relevancy/minimum redundancy method, the investigators reduced the number of sound features that were significantly different between the groups to two, "and unsupervised clustering of these showed an overall accuracy of 84%, with a sensitivity of 88% and a specificity of 80%," Dr. Moussavi reported.

"It is known that [OSA] patients have a smaller and more collapsible pharynx, which is compensated by increased dilator muscle activity during wakefulness. They tend to have more negative pharyngeal pressure, which can be detected via breathing sounds through the nose because of higher resistance," she said. Because breath sounds are directly related to pharyngeal pressure, "this method is sensitive to the severity of [OSA] even during wakefulness."

The study was supported by the National Sciences and Engineering Research Council of Canada and TRI Labs Winnipeg where Dr. Moussavi is an adjunct scientist.

MINNEAPOLIS – An automated analysis of tracheal breath sounds while awake was predictive of obstructive sleep apnea in a small study.

If validated in larger studies, the findings may streamline the obstructive sleep apnea (OSA) screening process, resulting in earlier diagnosis and treatment of severe cases, Zahra Moussavi, Ph.D., said at the annual meeting of the Associated Professional Sleep Societies. "The ability to predict the likelihood and severity of obstructive sleep apnea without performing overnight polysomnography is very appealing and would lead to significant reductions in health care costs, compared with full-night sleep assessments."

Obstructive sleep apnea (OSA) is highly prevalent in the general population, but only 30% of patients referred to a sleep lab for evaluation have severe OSA requiring treatment, said Dr. Moussavi, a professor in the department of electrical and computer engineering at the University of Manitoba, Winnipeg. With no fast, accurate, clinical or laboratory tools for predicting the severity of suspected OSA, full-night polysomnography is required to confirm the diagnosis and determine its severity. "Unfortunately, the demand [for full-night sleep studies] outweighs the available resources, resulting in appointment backlogs and long wait times, which can delay the initiation of potentially lifesaving care," she said.

Acoustic analysis has been used during sleep to evaluate the breathing and snoring patterns of suspected apnea patients. To examine wakeful breathing patterns associated with OSA, Dr. Moussavi and colleagues, recorded the tracheal breath sounds of 35 patients with varying severity of OSA and 17 age-matched controls.

"We recorded the tracheal breath sound in supine and upright positions during nose and mouth breathing," said Dr. Moussavi.

Spectral analysis of the respiratory signals indicated that variation in the average power of the tracheal breath sounds at different positions was a characteristic feature that discriminated the OSA and control groups.

Using the maximum relevancy/minimum redundancy method, the investigators reduced the number of sound features that were significantly different between the groups to two, "and unsupervised clustering of these showed an overall accuracy of 84%, with a sensitivity of 88% and a specificity of 80%," Dr. Moussavi reported.

"It is known that [OSA] patients have a smaller and more collapsible pharynx, which is compensated by increased dilator muscle activity during wakefulness. They tend to have more negative pharyngeal pressure, which can be detected via breathing sounds through the nose because of higher resistance," she said. Because breath sounds are directly related to pharyngeal pressure, "this method is sensitive to the severity of [OSA] even during wakefulness."

The study was supported by the National Sciences and Engineering Research Council of Canada and TRI Labs Winnipeg where Dr. Moussavi is an adjunct scientist.

MINNEAPOLIS – An automated analysis of tracheal breath sounds while awake was predictive of obstructive sleep apnea in a small study.

If validated in larger studies, the findings may streamline the obstructive sleep apnea (OSA) screening process, resulting in earlier diagnosis and treatment of severe cases, Zahra Moussavi, Ph.D., said at the annual meeting of the Associated Professional Sleep Societies. "The ability to predict the likelihood and severity of obstructive sleep apnea without performing overnight polysomnography is very appealing and would lead to significant reductions in health care costs, compared with full-night sleep assessments."

Obstructive sleep apnea (OSA) is highly prevalent in the general population, but only 30% of patients referred to a sleep lab for evaluation have severe OSA requiring treatment, said Dr. Moussavi, a professor in the department of electrical and computer engineering at the University of Manitoba, Winnipeg. With no fast, accurate, clinical or laboratory tools for predicting the severity of suspected OSA, full-night polysomnography is required to confirm the diagnosis and determine its severity. "Unfortunately, the demand [for full-night sleep studies] outweighs the available resources, resulting in appointment backlogs and long wait times, which can delay the initiation of potentially lifesaving care," she said.

Acoustic analysis has been used during sleep to evaluate the breathing and snoring patterns of suspected apnea patients. To examine wakeful breathing patterns associated with OSA, Dr. Moussavi and colleagues, recorded the tracheal breath sounds of 35 patients with varying severity of OSA and 17 age-matched controls.

"We recorded the tracheal breath sound in supine and upright positions during nose and mouth breathing," said Dr. Moussavi.

Spectral analysis of the respiratory signals indicated that variation in the average power of the tracheal breath sounds at different positions was a characteristic feature that discriminated the OSA and control groups.

Using the maximum relevancy/minimum redundancy method, the investigators reduced the number of sound features that were significantly different between the groups to two, "and unsupervised clustering of these showed an overall accuracy of 84%, with a sensitivity of 88% and a specificity of 80%," Dr. Moussavi reported.

"It is known that [OSA] patients have a smaller and more collapsible pharynx, which is compensated by increased dilator muscle activity during wakefulness. They tend to have more negative pharyngeal pressure, which can be detected via breathing sounds through the nose because of higher resistance," she said. Because breath sounds are directly related to pharyngeal pressure, "this method is sensitive to the severity of [OSA] even during wakefulness."

The study was supported by the National Sciences and Engineering Research Council of Canada and TRI Labs Winnipeg where Dr. Moussavi is an adjunct scientist.

Major Finding: The rate of severe disease flares in seropositive patients treated with belimumab decreased from 17% at year 1 to 5% at year 6 with no increase in the adverse event rate during that period.

Data Source: An open-label continuation study of a phase II randomized controlled trial of belimumab in patients with serologically active systemic lupus erythematosus to assess safety and efficacy at 6 years.

Disclosures: Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, said Dr. Michelle A. Petri, director of the lupus center at Johns Hopkins University, Baltimore. Belimumab inhibits B-lymphocyte stimulator. Among the “unanswered questions” about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug's safety over time, she said.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10-mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group (BILAG) 1A/2B flares, the SLE Responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. “Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1,” she said.

The SRI rate increased from 46% at year 1 to 55%–61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. “Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important,” she said.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, over baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, “especially in whom there is evidence that B cells are driving disease activity, such as anti-DNA or low complement,” she said.

Despite some study design flaws, the safety and tolerability data suggest that, in “the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy.”

Yet to be addressed “meaningfully” in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug's effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Major Finding: The rate of severe disease flares in seropositive patients treated with belimumab decreased from 17% at year 1 to 5% at year 6 with no increase in the adverse event rate during that period.

Data Source: An open-label continuation study of a phase II randomized controlled trial of belimumab in patients with serologically active systemic lupus erythematosus to assess safety and efficacy at 6 years.

Disclosures: Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, said Dr. Michelle A. Petri, director of the lupus center at Johns Hopkins University, Baltimore. Belimumab inhibits B-lymphocyte stimulator. Among the “unanswered questions” about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug's safety over time, she said.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10-mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group (BILAG) 1A/2B flares, the SLE Responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. “Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1,” she said.

The SRI rate increased from 46% at year 1 to 55%–61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. “Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important,” she said.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, over baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, “especially in whom there is evidence that B cells are driving disease activity, such as anti-DNA or low complement,” she said.

Despite some study design flaws, the safety and tolerability data suggest that, in “the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy.”

Yet to be addressed “meaningfully” in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug's effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

Major Finding: The rate of severe disease flares in seropositive patients treated with belimumab decreased from 17% at year 1 to 5% at year 6 with no increase in the adverse event rate during that period.

Data Source: An open-label continuation study of a phase II randomized controlled trial of belimumab in patients with serologically active systemic lupus erythematosus to assess safety and efficacy at 6 years.

Disclosures: Dr. Petri disclosed receiving research support and consultancy fees for Human Genome Sciences/GlaxoSmithKline.

LONDON – Belimumab therapy in patients with active systemic lupus erythematosus was well tolerated and associated with sustained disease improvement over 6 years, judging from the findings of a continuation study of a phase II randomized controlled trial.

Hyped regularly as the first new drug approved for the treatment of systemic lupus erythematosus (SLE) in 50 years, belimumab has been shown to reduce disease activity and flares in serologically active patients when combined with standard therapy versus placebo, said Dr. Michelle A. Petri, director of the lupus center at Johns Hopkins University, Baltimore. Belimumab inhibits B-lymphocyte stimulator. Among the “unanswered questions” about the recently approved monoclonal antibody, however, are the durability of the disease improvement and the drug's safety over time, she said.

To examine long-term safety and efficacy of the drug, Dr. Petri and her colleagues conducted a follow-up study of patients who participated in a 1-year phase II randomized controlled trial (Arthritis Rheum. 2009;61:1168-78) and who continued treatment for up to 6 years. After the randomized phase of the trial, all of the patients entered the open-label extension phase of the trial during which they were continued on one of three belimumab (Benlysta) doses – 1 mg/kg, 4 mg/kg, or 10 mg/kg. At study week 80, a total of 296 of the patients entered the continuation phase during which they all received 10-mg/kg doses of the drug, Dr. Petri explained. As of July 2010, a total of 200 patients remained in the study, she said.

Focusing specifically on the subset of seropositive SLE patients (positive for antineutrophil antibody or positive for anti–double-stranded DNA) in whom the B-cell–directed therapy is considered to be most effective, the investigators measured disease activity using the SLE Flare Index (SFI), the British Isles Lupus Assessment Group (BILAG) 1A/2B flares, the SLE Responder Index (SRI), and biomarkers (complement and autoantibodies), and assessed adverse events at each study visit, Dr. Petri said. “Over 6 years, patient response rates improved, the frequency of new flares decreased significantly, and the rate of adverse events remained stable or declined, compared to year 1,” she said.

The SRI rate increased from 46% at year 1 to 55%–61% through year 6; the frequency of 1 new BILAG A or 2 new B flares decreased from 35% at 1 year to 11% at year 6; and the frequency of SFI flares decreased from 76% at 1 year to 42% at year 6, Dr. Petri said. Additionally, the rate of severe flares, which was 17% at year 1, decreased to 5% at year 6. “Patients had to be really sick to get into this study in the first place, so to see the severe flares disappear to that degree is really clinically important,” she said.

The proportion of patients with increased complement 3 or 4 and decreased anti-Sm, anti–double-stranded DNA, and anticardiolipin antibodies increased over time, suggesting a sustained or improved therapeutic response, Dr. Petri said. Concomitant corticosteroid use decreased by a mean of 34% from baseline, with an absolute reduction of 4.7 mg/day at year 6, over baseline.

Belimumab is not indicated as a stand-alone, first-line therapy but rather as an adjunct therapy in patients who have not responded to the standard of care, “especially in whom there is evidence that B cells are driving disease activity, such as anti-DNA or low complement,” she said.

Despite some study design flaws, the safety and tolerability data suggest that, in “the appropriately targeted SLE population, belimumab has the potential to be a widely used, steroid-sparing background therapy.”

Yet to be addressed “meaningfully” in clinical trials are the safety and efficacy of belimumab in black patients, as well as the drug's effects on patients with lupus nephritis or central nervous system involvement – both of which were excluded from this and the pivotal trials that led to FDA approval of the drug – as well as pediatric and pregnant patients, Dr. Petri said in an interview.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

LONDON – The safety profile of tocilizumab in a prospective open-label study of rheumatoid arthritis patients with inadequate responses to biologics or disease-modifying antirheumatic drugs was comparable across the study’s monotherapy, dose-escalated combination therapy, and high-dose combination therapy treatment arms, Dr. Michael E. Weinblatt reported at the annual European Congress of Rheumatology.

This was the "first report of tocilizumab safety and efficacy in a real-world setting" in patients with disease progression, despite treatment with disease-modifying antirheumatic drugs (DMARDs) or biologic agents. The study found the overall safety of the interleukin-6 monoclonal antibody was consistent with that observed in extension studies of the drug’s pivotal phase III program, said Dr. Weinblatt, who is a professor of medicine at Harvard Medical School and codirector of clinical rheumatology at Brigham and Women’s Hospital in Boston.

Of the 836 patients enrolled in Access to Therapy-Safety Trial of Adalimumab in Rheumatoid Arthritis (ACT-STAR), 183 patients who were on a biologic drug only prior to baseline were assigned to 8mg/kg tocilizumab (Actemra) monotherapy every 4 weeks. Another 363 and 360 patients, respectively, who were on DMARDs only or in combination with biologics prior to baseline were randomized to dose-escalating tocilizumab (starting at 4 mg/kg and increasing up to 8 mg/kg at physicians’ discretion) in combination with one or more DMARD or to 8 mg/kg tocilizumab in combination with one or more DMARD, Dr. Weinblatt reported in a late-breaking abstract session.

As per study protocol, all biologic drugs were discontinued prior to baseline, and patients randomized to the dose-escalating tocilizumab/DMARD condition who did not achieve at least 20% improvement in tender and swollen joint count had their tocilizumab dose increased to 8mg/kg, while others in that group could have their dose increased to 8mg/kg at the investigator’s discretion, Dr. Weinblatt explained. Patients on 8mg/kg tocilizumab plus DMARD could have their dose decreased at any time for safety reasons, he noted. The study’s primary outcome was the number of patients who experienced serious adverse events during the study period.

There was no statistical difference in the rates of serious adverse events across all three arms, Dr. Weinblatt reported. In the tocilizumab monotherapy group, eight patients (5.8%) had serious adverse events, leading to three treatment discontinuations and one dose modification. In the dose-escalation arm, 29 (8%) serious adverse events were reported, leading to seven dose modifications and 11 treatment discontinuations. In the high-dose tocilizumab group, 32 (8.4%) serious adverse events led to 11 dose modifications and four treatment discontinuations, he said. Two deaths not related to treatment occurred in the dose escalation group, he noted.

Serious infections were the most common serious adverse event, occurring in 3.6%, 3.9%, and 2.9% of patients in the dose-escalating, high-dose, and monotherapy groups, respectively, Dr. Weinblatt said. There were no reports of tuberculosis in any of the patients, he said. Three nonfatal gastrointestinal perforations occurred in the dose-escalating combination group, "all in patients with comorbidities," he stressed.

A total of 42 patients had abnormal liver function tests, including 26 with liver tests that were twice the upper limit of normal, 14 with values three times the upper limit of normal, and 2 with values exceeding five times the upper limit of normal. These findings are "similar to the values observed in the phase III extension studies, said Dr. Weinblatt. There were no significant between-group differences in the rates of uncommon lab abnormalities, he said.

With respect to treatment efficacy, DAS28 remission and mean change from baseline, and ACR20/50/70 responses were similar across all of the groups, Dr. Weinblatt said. "The results confirm that what we’ve seen in the research program translates to the real-world setting, with similar safety and efficacy numbers," he said in an interview. They also point to the possibility of the drug being used as a first-line agent as rheumatologists become more comfortable with it, particularly if it receives FDA approval for use as monotherapy in patients who have failed DMARDs, he said.

Dr. Weinblatt disclosed financial relationships with Abbott, Centocor Ortho Biotech, and Pfizer/Wyeth.

SAN ANTONIO – Partial fundoplication improves dysphagia and regurgitation symptom scores in those patients undergoing laparoscopic Heller myotomy for esophageal achalasia, regardless of whether the fundus is laid over the anterior esophagus or wrapped around the back of it, a multicenter study has shown.

Previous studies have demonstrated that partial fundoplication minimizes the likelihood of developing gastroesophageal reflux disease (GERD), but none has systematically compared the risks and benefits associated with wrapping the gastric fundus anterior to the esophagus (Dor fundoplication) or posterior to the esophagus (Toupet fundoplication), Dr. Arthur Rawlings said at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

"The type of fundoplication that should be performed is controversial, and currently determined by surgeon’s choice rather than scientific evidence," he said. "Some surgeons advocate the Dor because they say it’s less complicated to perform, [avoids] the need for complete posterior dissection, completely disrupts the posterior esophageal ligament, and does cover the exposed esophageal mucosa." On the other hand, he noted, "other surgeons advocate for a Toupet fundoplication because it keeps the edges of the myotomy separated and possibly provides better reflux control."

To compare symptom frequency and severity as well as physiological differences associated with the two procedures, Dr. Rawlings of Washington University, St. Louis, and his colleagues conducted a multicenter, prospective trial. In all, 85 patients undergoing laparoscopic Heller myotomy at five sites in 2003-2008 were randomized to the Dor or Toupet partial fundoplication. The investigators assessed symptomatic GERD scores based on a 5-point (0-4) Likert scale preoperatively and at 2-6 weeks, 6 months, and 12 months postoperatively. They also evaluated 24-hour pH testing at 6-12 months, calculating the percentage of total pH time less than 4 and a composite DeMeester pH score, he said.

Both groups had similar age, sex distribution, and illness characteristics. The researchers obtained 6- to 12-month pH studies for 24 of the 49 patients who were randomized to the Dor procedure and 19 of the 36 patients who were randomized to the Toupet procedure, Dr. Rawlings said. The results reported at the meeting represent those obtained for the patients for whom pH-testing results were available, he explained.

In both groups, dysphagia and regurgitation symptom frequency and severity scores improved substantially, compared with preoperative measures, Dr. Rawlings said. "Statistically significant improvements were observed in both groups for all but heartburn and chest pain measures," he noted. Specifically, in the Dor group, the preoperative solid dysphagia, heartburn, and regurgitation scores of 3.0, 1.5, and 2.8, respectively, improved to 1.3, 0.7, and 0.7 at 6 months, and the preoperative scores in the Toupet group of 3.1, 1.0, and 3.3 improved to 1.0, 0.3, and 0.1, respectively, he said.

There was no significant difference between the two groups with respect to DeMeester pH scores or the percentage of pH time less than 4, although abnormal acid reflux was experienced by 42% of the Dor patients and just 21% of the Toupet patients, said Dr. Rawlings. The difference between the median DeMeester pH scores at 6 months for the Dor (7.2) and Toupet (2.2) groups did not reach statistical significance, he said.

In a subgroup analysis of individuals with abnormal reflux scores regardless of fundoplication procedure, "the only thing that fell out as significant was heartburn frequency and severity," Dr. Rawlings stated.

The findings indicate that both the Dor and Toupet procedures following Heller myotomy produce comparable decreases in reflux symptoms and improvements in quality of life, according to Dr. Rawlings. The differences in pathological acid reflux between the two groups, though not statistically significant, "do support the use of pH testing following Heller myotomy for detecting abnormal esophageal acid exposure," he said.

This study was supported a SAGES research grant. Dr. Rawlings disclosed financial relationships with Lifecell Corp. and Cook Medical.☐

SAN ANTONIO – Partial fundoplication improves dysphagia and regurgitation symptom scores in those patients undergoing laparoscopic Heller myotomy for esophageal achalasia, regardless of whether the fundus is laid over the anterior esophagus or wrapped around the back of it, a multicenter study has shown.

Previous studies have demonstrated that partial fundoplication minimizes the likelihood of developing gastroesophageal reflux disease (GERD), but none has systematically compared the risks and benefits associated with wrapping the gastric fundus anterior to the esophagus (Dor fundoplication) or posterior to the esophagus (Toupet fundoplication), Dr. Arthur Rawlings said at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

"The type of fundoplication that should be performed is controversial, and currently determined by surgeon’s choice rather than scientific evidence," he said. "Some surgeons advocate the Dor because they say it’s less complicated to perform, [avoids] the need for complete posterior dissection, completely disrupts the posterior esophageal ligament, and does cover the exposed esophageal mucosa." On the other hand, he noted, "other surgeons advocate for a Toupet fundoplication because it keeps the edges of the myotomy separated and possibly provides better reflux control."

To compare symptom frequency and severity as well as physiological differences associated with the two procedures, Dr. Rawlings of Washington University, St. Louis, and his colleagues conducted a multicenter, prospective trial. In all, 85 patients undergoing laparoscopic Heller myotomy at five sites in 2003-2008 were randomized to the Dor or Toupet partial fundoplication. The investigators assessed symptomatic GERD scores based on a 5-point (0-4) Likert scale preoperatively and at 2-6 weeks, 6 months, and 12 months postoperatively. They also evaluated 24-hour pH testing at 6-12 months, calculating the percentage of total pH time less than 4 and a composite DeMeester pH score, he said.

Both groups had similar age, sex distribution, and illness characteristics. The researchers obtained 6- to 12-month pH studies for 24 of the 49 patients who were randomized to the Dor procedure and 19 of the 36 patients who were randomized to the Toupet procedure, Dr. Rawlings said. The results reported at the meeting represent those obtained for the patients for whom pH-testing results were available, he explained.

In both groups, dysphagia and regurgitation symptom frequency and severity scores improved substantially, compared with preoperative measures, Dr. Rawlings said. "Statistically significant improvements were observed in both groups for all but heartburn and chest pain measures," he noted. Specifically, in the Dor group, the preoperative solid dysphagia, heartburn, and regurgitation scores of 3.0, 1.5, and 2.8, respectively, improved to 1.3, 0.7, and 0.7 at 6 months, and the preoperative scores in the Toupet group of 3.1, 1.0, and 3.3 improved to 1.0, 0.3, and 0.1, respectively, he said.

There was no significant difference between the two groups with respect to DeMeester pH scores or the percentage of pH time less than 4, although abnormal acid reflux was experienced by 42% of the Dor patients and just 21% of the Toupet patients, said Dr. Rawlings. The difference between the median DeMeester pH scores at 6 months for the Dor (7.2) and Toupet (2.2) groups did not reach statistical significance, he said.

In a subgroup analysis of individuals with abnormal reflux scores regardless of fundoplication procedure, "the only thing that fell out as significant was heartburn frequency and severity," Dr. Rawlings stated.

The findings indicate that both the Dor and Toupet procedures following Heller myotomy produce comparable decreases in reflux symptoms and improvements in quality of life, according to Dr. Rawlings. The differences in pathological acid reflux between the two groups, though not statistically significant, "do support the use of pH testing following Heller myotomy for detecting abnormal esophageal acid exposure," he said.

This study was supported a SAGES research grant. Dr. Rawlings disclosed financial relationships with Lifecell Corp. and Cook Medical.☐

SAN ANTONIO – Partial fundoplication improves dysphagia and regurgitation symptom scores in those patients undergoing laparoscopic Heller myotomy for esophageal achalasia, regardless of whether the fundus is laid over the anterior esophagus or wrapped around the back of it, a multicenter study has shown.

Previous studies have demonstrated that partial fundoplication minimizes the likelihood of developing gastroesophageal reflux disease (GERD), but none has systematically compared the risks and benefits associated with wrapping the gastric fundus anterior to the esophagus (Dor fundoplication) or posterior to the esophagus (Toupet fundoplication), Dr. Arthur Rawlings said at the annual meeting of the Society of American Gastrointestinal and Endoscopic Surgeons.

"The type of fundoplication that should be performed is controversial, and currently determined by surgeon’s choice rather than scientific evidence," he said. "Some surgeons advocate the Dor because they say it’s less complicated to perform, [avoids] the need for complete posterior dissection, completely disrupts the posterior esophageal ligament, and does cover the exposed esophageal mucosa." On the other hand, he noted, "other surgeons advocate for a Toupet fundoplication because it keeps the edges of the myotomy separated and possibly provides better reflux control."

To compare symptom frequency and severity as well as physiological differences associated with the two procedures, Dr. Rawlings of Washington University, St. Louis, and his colleagues conducted a multicenter, prospective trial. In all, 85 patients undergoing laparoscopic Heller myotomy at five sites in 2003-2008 were randomized to the Dor or Toupet partial fundoplication. The investigators assessed symptomatic GERD scores based on a 5-point (0-4) Likert scale preoperatively and at 2-6 weeks, 6 months, and 12 months postoperatively. They also evaluated 24-hour pH testing at 6-12 months, calculating the percentage of total pH time less than 4 and a composite DeMeester pH score, he said.

Both groups had similar age, sex distribution, and illness characteristics. The researchers obtained 6- to 12-month pH studies for 24 of the 49 patients who were randomized to the Dor procedure and 19 of the 36 patients who were randomized to the Toupet procedure, Dr. Rawlings said. The results reported at the meeting represent those obtained for the patients for whom pH-testing results were available, he explained.

In both groups, dysphagia and regurgitation symptom frequency and severity scores improved substantially, compared with preoperative measures, Dr. Rawlings said. "Statistically significant improvements were observed in both groups for all but heartburn and chest pain measures," he noted. Specifically, in the Dor group, the preoperative solid dysphagia, heartburn, and regurgitation scores of 3.0, 1.5, and 2.8, respectively, improved to 1.3, 0.7, and 0.7 at 6 months, and the preoperative scores in the Toupet group of 3.1, 1.0, and 3.3 improved to 1.0, 0.3, and 0.1, respectively, he said.

There was no significant difference between the two groups with respect to DeMeester pH scores or the percentage of pH time less than 4, although abnormal acid reflux was experienced by 42% of the Dor patients and just 21% of the Toupet patients, said Dr. Rawlings. The difference between the median DeMeester pH scores at 6 months for the Dor (7.2) and Toupet (2.2) groups did not reach statistical significance, he said.

In a subgroup analysis of individuals with abnormal reflux scores regardless of fundoplication procedure, "the only thing that fell out as significant was heartburn frequency and severity," Dr. Rawlings stated.

The findings indicate that both the Dor and Toupet procedures following Heller myotomy produce comparable decreases in reflux symptoms and improvements in quality of life, according to Dr. Rawlings. The differences in pathological acid reflux between the two groups, though not statistically significant, "do support the use of pH testing following Heller myotomy for detecting abnormal esophageal acid exposure," he said.

This study was supported a SAGES research grant. Dr. Rawlings disclosed financial relationships with Lifecell Corp. and Cook Medical.☐