User login
B-Cell Depletion May Benefit Sjögren's Patients
SAN ANTONIO — The lengthening list of potential uses for rituximab may soon include the treatment of early and active Sjögren's syndrome—but with a caution.
In Sjögren's syndrome, high levels of B-cell autoreactivity are associated with high disease activity, systemic complications, and a markedly elevated risk for the development of B-cell lymphoma, Justin Pijpe, M.D., said at the annual meeting of the American College of Rheumatology.
Current treatment approaches for the autoimmune disease, including corticosteroids and hydroxychloroquine, have been largely unsuccessful in alleviating symptoms and have no impact on the course of disease.
Rituximab (Rituxan) is a monoclonal antibody that binds to the CD20 receptor on B cells, leading to B-cell depletion. The drug is now being investigated in a phase I/II study to determine if B-cell depletion may be a beneficial approach in Sjögren's syndrome, Dr. Pijpe reported in a poster session.
To date, six patients, all female and whose mean age is 50 years, have been treated with four infusions of rituximab, 375 mg/m
All had early disease that was characterized by B-cell hyperactivity, with IgG levels exceeding 15 g/L and had the autoantibodies IgM-Rf and anti-SSA/B. Patients with early disease—4 years' duration or less—typically still have substantial residual exocrine gland function, he explained.
Preliminary data on clinical efficacy suggest marked subjective improvement of fatigue, sicca complaints, and health status, as well as an increase in salivary gland function, said Dr. Pijpe of University Hospital Groningen (the Netherlands).
Analysis of saliva showed a decrease in inflammatory activity, and lacrimal gland function was unchanged or showed slight improvement.
Serologic analysis revealed a decrease in erythrocyte sedimentation rate and rheumatoid factor level, and levels of IgG remained stable or decreased.
Repeat biopsies of the parotid glands showed an increase in IgA:IgG plasma cell ratio, suggesting a specific decrease in IgG-producing B cells in the affected tissue.
Rituximab seems to be very effective in the treatment of early Sjögren's syndrome, Dr. Pijpe said.
But further investigation is needed, given that two patients developed a serum sickness-like clinical picture, necessitating treatment cessation.
“I was very surprised, because this type of adverse event is very rare,” he said. “Our patients showed a clinical presentation compatible with serum sickness, but serologic analysis was not fully characteristic for a type III hypersensitivity reaction,” he told this newspaper.
For example, there was no proteinuria, and the one patient who was tested for human antichimeric antibodies was negative.
On the other hand, there was an acute phase response and a slight increase of C3d in both patients, findings that are indicative of complement consumption, he said.
This type of reaction has not been reported in recent studies of rituximab in systemic lupus erythematosus and rheumatoid arthritis.
Only three cases of serum sickness after rituximab treatment have been reported previously, he said.
SAN ANTONIO — The lengthening list of potential uses for rituximab may soon include the treatment of early and active Sjögren's syndrome—but with a caution.
In Sjögren's syndrome, high levels of B-cell autoreactivity are associated with high disease activity, systemic complications, and a markedly elevated risk for the development of B-cell lymphoma, Justin Pijpe, M.D., said at the annual meeting of the American College of Rheumatology.
Current treatment approaches for the autoimmune disease, including corticosteroids and hydroxychloroquine, have been largely unsuccessful in alleviating symptoms and have no impact on the course of disease.
Rituximab (Rituxan) is a monoclonal antibody that binds to the CD20 receptor on B cells, leading to B-cell depletion. The drug is now being investigated in a phase I/II study to determine if B-cell depletion may be a beneficial approach in Sjögren's syndrome, Dr. Pijpe reported in a poster session.
To date, six patients, all female and whose mean age is 50 years, have been treated with four infusions of rituximab, 375 mg/m
All had early disease that was characterized by B-cell hyperactivity, with IgG levels exceeding 15 g/L and had the autoantibodies IgM-Rf and anti-SSA/B. Patients with early disease—4 years' duration or less—typically still have substantial residual exocrine gland function, he explained.
Preliminary data on clinical efficacy suggest marked subjective improvement of fatigue, sicca complaints, and health status, as well as an increase in salivary gland function, said Dr. Pijpe of University Hospital Groningen (the Netherlands).
Analysis of saliva showed a decrease in inflammatory activity, and lacrimal gland function was unchanged or showed slight improvement.
Serologic analysis revealed a decrease in erythrocyte sedimentation rate and rheumatoid factor level, and levels of IgG remained stable or decreased.
Repeat biopsies of the parotid glands showed an increase in IgA:IgG plasma cell ratio, suggesting a specific decrease in IgG-producing B cells in the affected tissue.
Rituximab seems to be very effective in the treatment of early Sjögren's syndrome, Dr. Pijpe said.
But further investigation is needed, given that two patients developed a serum sickness-like clinical picture, necessitating treatment cessation.
“I was very surprised, because this type of adverse event is very rare,” he said. “Our patients showed a clinical presentation compatible with serum sickness, but serologic analysis was not fully characteristic for a type III hypersensitivity reaction,” he told this newspaper.
For example, there was no proteinuria, and the one patient who was tested for human antichimeric antibodies was negative.
On the other hand, there was an acute phase response and a slight increase of C3d in both patients, findings that are indicative of complement consumption, he said.
This type of reaction has not been reported in recent studies of rituximab in systemic lupus erythematosus and rheumatoid arthritis.
Only three cases of serum sickness after rituximab treatment have been reported previously, he said.
SAN ANTONIO — The lengthening list of potential uses for rituximab may soon include the treatment of early and active Sjögren's syndrome—but with a caution.
In Sjögren's syndrome, high levels of B-cell autoreactivity are associated with high disease activity, systemic complications, and a markedly elevated risk for the development of B-cell lymphoma, Justin Pijpe, M.D., said at the annual meeting of the American College of Rheumatology.
Current treatment approaches for the autoimmune disease, including corticosteroids and hydroxychloroquine, have been largely unsuccessful in alleviating symptoms and have no impact on the course of disease.
Rituximab (Rituxan) is a monoclonal antibody that binds to the CD20 receptor on B cells, leading to B-cell depletion. The drug is now being investigated in a phase I/II study to determine if B-cell depletion may be a beneficial approach in Sjögren's syndrome, Dr. Pijpe reported in a poster session.
To date, six patients, all female and whose mean age is 50 years, have been treated with four infusions of rituximab, 375 mg/m
All had early disease that was characterized by B-cell hyperactivity, with IgG levels exceeding 15 g/L and had the autoantibodies IgM-Rf and anti-SSA/B. Patients with early disease—4 years' duration or less—typically still have substantial residual exocrine gland function, he explained.
Preliminary data on clinical efficacy suggest marked subjective improvement of fatigue, sicca complaints, and health status, as well as an increase in salivary gland function, said Dr. Pijpe of University Hospital Groningen (the Netherlands).
Analysis of saliva showed a decrease in inflammatory activity, and lacrimal gland function was unchanged or showed slight improvement.
Serologic analysis revealed a decrease in erythrocyte sedimentation rate and rheumatoid factor level, and levels of IgG remained stable or decreased.
Repeat biopsies of the parotid glands showed an increase in IgA:IgG plasma cell ratio, suggesting a specific decrease in IgG-producing B cells in the affected tissue.
Rituximab seems to be very effective in the treatment of early Sjögren's syndrome, Dr. Pijpe said.
But further investigation is needed, given that two patients developed a serum sickness-like clinical picture, necessitating treatment cessation.
“I was very surprised, because this type of adverse event is very rare,” he said. “Our patients showed a clinical presentation compatible with serum sickness, but serologic analysis was not fully characteristic for a type III hypersensitivity reaction,” he told this newspaper.
For example, there was no proteinuria, and the one patient who was tested for human antichimeric antibodies was negative.
On the other hand, there was an acute phase response and a slight increase of C3d in both patients, findings that are indicative of complement consumption, he said.
This type of reaction has not been reported in recent studies of rituximab in systemic lupus erythematosus and rheumatoid arthritis.
Only three cases of serum sickness after rituximab treatment have been reported previously, he said.
When Bosentan Treatment Fails, Sitaxsentan May Help
SAN ANTONIO — Pulmonary arterial hypertension patients treated with bosentan whose condition deteriorates or who can't tolerate the drug may respond to a related medicine, sitaxsentan, a preliminary study suggests.
Like bosentan, sitaxsentan is an endothelin receptor antagonist, but it is much more selective for endothelin A. Bosentan blocks the activity of both endothelin A and endothelin B.
Endothelin is a potent endogenous peptide with vasoconstricting, mitogenic, and profibrotic effects. It appears to play a role in the pathology of pulmonary arterial hypertension associated with connective tissue disease.
“Although the relative importance of endothelin A versus endothelin B in pulmonary arterial hypertension remains unclear, selective antagonism of endothelin A may be advantageous in blocking the deleterious endothelin A vasoconstriction in the pulmonary vasculature while maintaining the vasodilator and clearance functions of the endothelin B receptor,” Adaani Frost, M.D., said in a poster session at the annual meeting of the American College of Rheumatology.
Although bosentan (Tracleer) has proven beneficial in this condition, many patients develop liver function abnormalities during treatment. Bosentan is metabolized by the liver, and the elevations in liver enzymes are thought to relate to an accumulation of bile salts. Sitaxsentan undergoes both hepatic and renal metabolism, and has no effect on bile salts or bilirubin, Dr. Frost explained.
In an effort to determine if the selective endothelin antagonist would provide an effective alternative to bosentan, 11 patients were enrolled in an open‐label study. Of these, three had developed liver function abnormalities, and eight experienced clinical deterioration during bosentan treatment. One patient who was New York Heart Association functional class IV at study entry died after 5 weeks of treatment with sitaxsentan and was not included in the analysis.
The remaining 10 have now been followed for 12 weeks. The mean improvement in 6‐minute walk time with sitaxsentan was 36.5 meters. Although the condition of four patients improved, five stabilized, and one's condition deteriorated, said Dr. Frost, professor of medicine, Baylor College of Medicine, Houston.
None of the patients who experienced liver function abnormalities on bosentan did so on sitaxsentan. One patient whose condition had deteriorated clinically experienced transient liver function abnormalities that resolved spontaneously and did not require cessation of the drug.
Ongoing studies should provide further information on using sitaxsentan in this population, Dr. Frost said.
The study was undertaken with a research grant from Encysive Pharmaceuticals, Bellaire, Tex.
SAN ANTONIO — Pulmonary arterial hypertension patients treated with bosentan whose condition deteriorates or who can't tolerate the drug may respond to a related medicine, sitaxsentan, a preliminary study suggests.
Like bosentan, sitaxsentan is an endothelin receptor antagonist, but it is much more selective for endothelin A. Bosentan blocks the activity of both endothelin A and endothelin B.
Endothelin is a potent endogenous peptide with vasoconstricting, mitogenic, and profibrotic effects. It appears to play a role in the pathology of pulmonary arterial hypertension associated with connective tissue disease.
“Although the relative importance of endothelin A versus endothelin B in pulmonary arterial hypertension remains unclear, selective antagonism of endothelin A may be advantageous in blocking the deleterious endothelin A vasoconstriction in the pulmonary vasculature while maintaining the vasodilator and clearance functions of the endothelin B receptor,” Adaani Frost, M.D., said in a poster session at the annual meeting of the American College of Rheumatology.
Although bosentan (Tracleer) has proven beneficial in this condition, many patients develop liver function abnormalities during treatment. Bosentan is metabolized by the liver, and the elevations in liver enzymes are thought to relate to an accumulation of bile salts. Sitaxsentan undergoes both hepatic and renal metabolism, and has no effect on bile salts or bilirubin, Dr. Frost explained.
In an effort to determine if the selective endothelin antagonist would provide an effective alternative to bosentan, 11 patients were enrolled in an open‐label study. Of these, three had developed liver function abnormalities, and eight experienced clinical deterioration during bosentan treatment. One patient who was New York Heart Association functional class IV at study entry died after 5 weeks of treatment with sitaxsentan and was not included in the analysis.
The remaining 10 have now been followed for 12 weeks. The mean improvement in 6‐minute walk time with sitaxsentan was 36.5 meters. Although the condition of four patients improved, five stabilized, and one's condition deteriorated, said Dr. Frost, professor of medicine, Baylor College of Medicine, Houston.
None of the patients who experienced liver function abnormalities on bosentan did so on sitaxsentan. One patient whose condition had deteriorated clinically experienced transient liver function abnormalities that resolved spontaneously and did not require cessation of the drug.
Ongoing studies should provide further information on using sitaxsentan in this population, Dr. Frost said.
The study was undertaken with a research grant from Encysive Pharmaceuticals, Bellaire, Tex.
SAN ANTONIO — Pulmonary arterial hypertension patients treated with bosentan whose condition deteriorates or who can't tolerate the drug may respond to a related medicine, sitaxsentan, a preliminary study suggests.
Like bosentan, sitaxsentan is an endothelin receptor antagonist, but it is much more selective for endothelin A. Bosentan blocks the activity of both endothelin A and endothelin B.
Endothelin is a potent endogenous peptide with vasoconstricting, mitogenic, and profibrotic effects. It appears to play a role in the pathology of pulmonary arterial hypertension associated with connective tissue disease.
“Although the relative importance of endothelin A versus endothelin B in pulmonary arterial hypertension remains unclear, selective antagonism of endothelin A may be advantageous in blocking the deleterious endothelin A vasoconstriction in the pulmonary vasculature while maintaining the vasodilator and clearance functions of the endothelin B receptor,” Adaani Frost, M.D., said in a poster session at the annual meeting of the American College of Rheumatology.
Although bosentan (Tracleer) has proven beneficial in this condition, many patients develop liver function abnormalities during treatment. Bosentan is metabolized by the liver, and the elevations in liver enzymes are thought to relate to an accumulation of bile salts. Sitaxsentan undergoes both hepatic and renal metabolism, and has no effect on bile salts or bilirubin, Dr. Frost explained.
In an effort to determine if the selective endothelin antagonist would provide an effective alternative to bosentan, 11 patients were enrolled in an open‐label study. Of these, three had developed liver function abnormalities, and eight experienced clinical deterioration during bosentan treatment. One patient who was New York Heart Association functional class IV at study entry died after 5 weeks of treatment with sitaxsentan and was not included in the analysis.
The remaining 10 have now been followed for 12 weeks. The mean improvement in 6‐minute walk time with sitaxsentan was 36.5 meters. Although the condition of four patients improved, five stabilized, and one's condition deteriorated, said Dr. Frost, professor of medicine, Baylor College of Medicine, Houston.
None of the patients who experienced liver function abnormalities on bosentan did so on sitaxsentan. One patient whose condition had deteriorated clinically experienced transient liver function abnormalities that resolved spontaneously and did not require cessation of the drug.
Ongoing studies should provide further information on using sitaxsentan in this population, Dr. Frost said.
The study was undertaken with a research grant from Encysive Pharmaceuticals, Bellaire, Tex.
Parathyroid Hormone Prevents First Fractures
SAN ANTONIO — Intact human recombinant parathyroid hormone prevented both recurrent and first fractures in a multinational, randomized, placebo-controlled study of postmenopausal women with osteoporosis, Mark P. Ettinger, M.D., said at the annual meeting of the American College of Rheumatology.
Previous studies have shown that the parathyroid hormone (PTH) analog teriperatide can prevent fractures in patients with advanced disease who already have had a fracture. The Treatment of Osteoporosis With PTH (TOP) study was the first to demonstrate the prevention of first fractures in patients with earlier disease, Dr. Ettinger said.
“This is extremely important, because the presence of any existing fracture greatly increases the risk of subsequent fractures,” he said in a late-breaking abstract session.
The TOP study included 2,532 women whose mean age was 64.4 years and whose mean spine, total hip, and femoral neck bone mineral density (BMD) T-scores were −3.0, −1.9, and −2.2, respectively.
The study population was very different from other osteoporosis treatment cohorts, in that the patients were younger, and only 19% already had fractures. In previous PTH phase II and teriperatide phase III trials, fracture prevalence ranged from 37% to 100%, he said.
Patients were randomized to 100 mcg subcutaneous PTH daily or placebo. All patients also took 700 mg calcium and 400 U vitamin D each day.
A total of 1,737 patients—72% and 65% of the placebo and PTH groups, respectively—completed the 18-month study.
At study completion, the vertebral fracture incidence was 3.33% in the placebo group and 1.14% in the PTH group, which represented a relative fracture risk reduction of 66%, said Dr. Ettinger, medical director emeritus of Radiant Research, Stuart, Fla.
In a per-protocol analysis, patients who had a fracture before entering the study had a 69% relative fracture risk reduction; those without a previous fracture had a risk reduction of 63%.
At month 18 the mean spine, total hip, and femoral neck BMD had increased by 7.2%, 2.2%, and 2.5%, respectively, in the PTH group relative to the placebo group, he said. This included patients allowed to take PTH on a less-than-daily schedule.
About 9% of the PTH group withdrew because of headache, dizziness, nausea, or vomiting, or elevated serum or urine calcium levels. Overall, 16% of PTH patients and 12% of placebo patients withdrew during the course of the study. There were two deaths in the placebo group and one in the PTH group; this was judged to be unrelated to treatment.
“The results of the TOP study may change our treatment paradigm somewhat and shift our target population to younger patients or those with less severe disease someday,” Dr. Ettinger told this newspaper. The recommended use for anabolic agents such as PTH and its analogs is to give them for 18–24 months, after which an antiresorptive agent, such as a bisphosphonate, is given to preserve the gains, continue improvement of bone density and quality, and continue mineralization.
Bisphosphonates are not given concurrently with PTH because they tend to blunt the response to PTH, at least for the first 6 months, he said. More information is needed as to how much blunting might occur with less potent antiresorptives, such as estrogen or raloxifene.
PTH (1–84) is a recombinant molecule with 84 amino acids in its peptide chain; teriperatide is a structural analog with the first 34 amino acids in its peptide chain.
Dr. Ettinger disclosed that he received research grants and consulting fees from many pharmaceutical companies including NPS Pharmaceuticals, the Salt Lake City-based manufacturer of PTH. An expanded new drug application package for the company's proprietary formulation, Preos, is planned for February 2005, according to the NPS Web site.
SAN ANTONIO — Intact human recombinant parathyroid hormone prevented both recurrent and first fractures in a multinational, randomized, placebo-controlled study of postmenopausal women with osteoporosis, Mark P. Ettinger, M.D., said at the annual meeting of the American College of Rheumatology.
Previous studies have shown that the parathyroid hormone (PTH) analog teriperatide can prevent fractures in patients with advanced disease who already have had a fracture. The Treatment of Osteoporosis With PTH (TOP) study was the first to demonstrate the prevention of first fractures in patients with earlier disease, Dr. Ettinger said.
“This is extremely important, because the presence of any existing fracture greatly increases the risk of subsequent fractures,” he said in a late-breaking abstract session.
The TOP study included 2,532 women whose mean age was 64.4 years and whose mean spine, total hip, and femoral neck bone mineral density (BMD) T-scores were −3.0, −1.9, and −2.2, respectively.
The study population was very different from other osteoporosis treatment cohorts, in that the patients were younger, and only 19% already had fractures. In previous PTH phase II and teriperatide phase III trials, fracture prevalence ranged from 37% to 100%, he said.
Patients were randomized to 100 mcg subcutaneous PTH daily or placebo. All patients also took 700 mg calcium and 400 U vitamin D each day.
A total of 1,737 patients—72% and 65% of the placebo and PTH groups, respectively—completed the 18-month study.
At study completion, the vertebral fracture incidence was 3.33% in the placebo group and 1.14% in the PTH group, which represented a relative fracture risk reduction of 66%, said Dr. Ettinger, medical director emeritus of Radiant Research, Stuart, Fla.
In a per-protocol analysis, patients who had a fracture before entering the study had a 69% relative fracture risk reduction; those without a previous fracture had a risk reduction of 63%.
At month 18 the mean spine, total hip, and femoral neck BMD had increased by 7.2%, 2.2%, and 2.5%, respectively, in the PTH group relative to the placebo group, he said. This included patients allowed to take PTH on a less-than-daily schedule.
About 9% of the PTH group withdrew because of headache, dizziness, nausea, or vomiting, or elevated serum or urine calcium levels. Overall, 16% of PTH patients and 12% of placebo patients withdrew during the course of the study. There were two deaths in the placebo group and one in the PTH group; this was judged to be unrelated to treatment.
“The results of the TOP study may change our treatment paradigm somewhat and shift our target population to younger patients or those with less severe disease someday,” Dr. Ettinger told this newspaper. The recommended use for anabolic agents such as PTH and its analogs is to give them for 18–24 months, after which an antiresorptive agent, such as a bisphosphonate, is given to preserve the gains, continue improvement of bone density and quality, and continue mineralization.
Bisphosphonates are not given concurrently with PTH because they tend to blunt the response to PTH, at least for the first 6 months, he said. More information is needed as to how much blunting might occur with less potent antiresorptives, such as estrogen or raloxifene.
PTH (1–84) is a recombinant molecule with 84 amino acids in its peptide chain; teriperatide is a structural analog with the first 34 amino acids in its peptide chain.
Dr. Ettinger disclosed that he received research grants and consulting fees from many pharmaceutical companies including NPS Pharmaceuticals, the Salt Lake City-based manufacturer of PTH. An expanded new drug application package for the company's proprietary formulation, Preos, is planned for February 2005, according to the NPS Web site.
SAN ANTONIO — Intact human recombinant parathyroid hormone prevented both recurrent and first fractures in a multinational, randomized, placebo-controlled study of postmenopausal women with osteoporosis, Mark P. Ettinger, M.D., said at the annual meeting of the American College of Rheumatology.
Previous studies have shown that the parathyroid hormone (PTH) analog teriperatide can prevent fractures in patients with advanced disease who already have had a fracture. The Treatment of Osteoporosis With PTH (TOP) study was the first to demonstrate the prevention of first fractures in patients with earlier disease, Dr. Ettinger said.
“This is extremely important, because the presence of any existing fracture greatly increases the risk of subsequent fractures,” he said in a late-breaking abstract session.
The TOP study included 2,532 women whose mean age was 64.4 years and whose mean spine, total hip, and femoral neck bone mineral density (BMD) T-scores were −3.0, −1.9, and −2.2, respectively.
The study population was very different from other osteoporosis treatment cohorts, in that the patients were younger, and only 19% already had fractures. In previous PTH phase II and teriperatide phase III trials, fracture prevalence ranged from 37% to 100%, he said.
Patients were randomized to 100 mcg subcutaneous PTH daily or placebo. All patients also took 700 mg calcium and 400 U vitamin D each day.
A total of 1,737 patients—72% and 65% of the placebo and PTH groups, respectively—completed the 18-month study.
At study completion, the vertebral fracture incidence was 3.33% in the placebo group and 1.14% in the PTH group, which represented a relative fracture risk reduction of 66%, said Dr. Ettinger, medical director emeritus of Radiant Research, Stuart, Fla.
In a per-protocol analysis, patients who had a fracture before entering the study had a 69% relative fracture risk reduction; those without a previous fracture had a risk reduction of 63%.
At month 18 the mean spine, total hip, and femoral neck BMD had increased by 7.2%, 2.2%, and 2.5%, respectively, in the PTH group relative to the placebo group, he said. This included patients allowed to take PTH on a less-than-daily schedule.
About 9% of the PTH group withdrew because of headache, dizziness, nausea, or vomiting, or elevated serum or urine calcium levels. Overall, 16% of PTH patients and 12% of placebo patients withdrew during the course of the study. There were two deaths in the placebo group and one in the PTH group; this was judged to be unrelated to treatment.
“The results of the TOP study may change our treatment paradigm somewhat and shift our target population to younger patients or those with less severe disease someday,” Dr. Ettinger told this newspaper. The recommended use for anabolic agents such as PTH and its analogs is to give them for 18–24 months, after which an antiresorptive agent, such as a bisphosphonate, is given to preserve the gains, continue improvement of bone density and quality, and continue mineralization.
Bisphosphonates are not given concurrently with PTH because they tend to blunt the response to PTH, at least for the first 6 months, he said. More information is needed as to how much blunting might occur with less potent antiresorptives, such as estrogen or raloxifene.
PTH (1–84) is a recombinant molecule with 84 amino acids in its peptide chain; teriperatide is a structural analog with the first 34 amino acids in its peptide chain.
Dr. Ettinger disclosed that he received research grants and consulting fees from many pharmaceutical companies including NPS Pharmaceuticals, the Salt Lake City-based manufacturer of PTH. An expanded new drug application package for the company's proprietary formulation, Preos, is planned for February 2005, according to the NPS Web site.
Acupuncture Improves Headache, Neck Pain : The modality is put to the test in trials involving 15,000 headache and 13,000 neck pain patients.
EXETER, ENGLAND–Data emerging from a large German research initiative sponsored by that country's insurance companies continue to support the use of acupuncture in the treatment of chronic pain conditions.
Two reports from the Acupuncture in Routine Care (ARC) study, presented at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth, demonstrated statistically significant and clinically relevant benefits for acupuncture when used in addition to routine care for headache and neck pain.
A total of 15,056 patients with migraine or tension-type headache were enrolled in the ARC headache study and randomly allocated to receive up to 15 acupuncture treatments during a 3-month period along with conventional treatment with analgesics, or to a control group receiving conventional treatment but no acupuncture.
Patients who did not agree to randomization received acupuncture and were monitored as a third group, said Susanne Jena, M.D., of the Institute for Social Medicine, Charité Medical Center, Berlin.
Three-quarters of the patients were female, and their mean age was 44 years. Of the 3,182 who agreed to randomization, 1,613 were in the acupuncture group and 1,569 were in the control group.
After 3 months of treatment, the frequency of headache days per month decreased from 8.4 days to 4.7 days in the two acupuncture groups, a significantly greater reduction than in the control group (8.1 days per month before treatment and 7.5 days per month post treatment).
The data also were analyzed according to headache type. Patients with migraine had an average of 7 days per month with headache before treatment and 4 days per month with headache after treatment including acupuncture. For those patients with tension-type headache, the average decreased from 10 days per month with headache before treatment to 5 days per month after, she said.
The improvements persisted for the next 3 months, she said.
Among the control group, 70% of patients required concomitant treatment with analgesics, compared with 50% of patients in the acupuncture groups.
The second report, which came from the ARC neck pain study, found similar results among 13,846 patients with chronic neck pain. In this cohort, 68% of whom were women with a mean age of 53 years, 1,753 were randomized to receive acupuncture, 1,698 served as controls, and 10,395 who had declined randomization also received acupuncture.
After 3 months of treatment, improvements on the neck pain disability score were more pronounced in the acupuncture groups than in the control group, said Claudia Becker-Witt, M.D., also with Charité. Scores fell from 56.4 to 39.6 in the acupuncture groups and from 54.5 to 51.2 in the control group, a statistically significant difference.
In both studies, the acupuncture groups also experienced significantly greater improvements in quality of life.
About 8%–9% of patients in both studies experienced side effects from acupuncture; they were not life threatening.
Analyses of cost-effectiveness and overall health benefits are being done, Dr. Becker-Witt said.
EXETER, ENGLAND–Data emerging from a large German research initiative sponsored by that country's insurance companies continue to support the use of acupuncture in the treatment of chronic pain conditions.
Two reports from the Acupuncture in Routine Care (ARC) study, presented at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth, demonstrated statistically significant and clinically relevant benefits for acupuncture when used in addition to routine care for headache and neck pain.
A total of 15,056 patients with migraine or tension-type headache were enrolled in the ARC headache study and randomly allocated to receive up to 15 acupuncture treatments during a 3-month period along with conventional treatment with analgesics, or to a control group receiving conventional treatment but no acupuncture.
Patients who did not agree to randomization received acupuncture and were monitored as a third group, said Susanne Jena, M.D., of the Institute for Social Medicine, Charité Medical Center, Berlin.
Three-quarters of the patients were female, and their mean age was 44 years. Of the 3,182 who agreed to randomization, 1,613 were in the acupuncture group and 1,569 were in the control group.
After 3 months of treatment, the frequency of headache days per month decreased from 8.4 days to 4.7 days in the two acupuncture groups, a significantly greater reduction than in the control group (8.1 days per month before treatment and 7.5 days per month post treatment).
The data also were analyzed according to headache type. Patients with migraine had an average of 7 days per month with headache before treatment and 4 days per month with headache after treatment including acupuncture. For those patients with tension-type headache, the average decreased from 10 days per month with headache before treatment to 5 days per month after, she said.
The improvements persisted for the next 3 months, she said.
Among the control group, 70% of patients required concomitant treatment with analgesics, compared with 50% of patients in the acupuncture groups.
The second report, which came from the ARC neck pain study, found similar results among 13,846 patients with chronic neck pain. In this cohort, 68% of whom were women with a mean age of 53 years, 1,753 were randomized to receive acupuncture, 1,698 served as controls, and 10,395 who had declined randomization also received acupuncture.
After 3 months of treatment, improvements on the neck pain disability score were more pronounced in the acupuncture groups than in the control group, said Claudia Becker-Witt, M.D., also with Charité. Scores fell from 56.4 to 39.6 in the acupuncture groups and from 54.5 to 51.2 in the control group, a statistically significant difference.
In both studies, the acupuncture groups also experienced significantly greater improvements in quality of life.
About 8%–9% of patients in both studies experienced side effects from acupuncture; they were not life threatening.
Analyses of cost-effectiveness and overall health benefits are being done, Dr. Becker-Witt said.
EXETER, ENGLAND–Data emerging from a large German research initiative sponsored by that country's insurance companies continue to support the use of acupuncture in the treatment of chronic pain conditions.
Two reports from the Acupuncture in Routine Care (ARC) study, presented at a symposium on alternative and complementary therapies sponsored by the universities of Exeter and Plymouth, demonstrated statistically significant and clinically relevant benefits for acupuncture when used in addition to routine care for headache and neck pain.
A total of 15,056 patients with migraine or tension-type headache were enrolled in the ARC headache study and randomly allocated to receive up to 15 acupuncture treatments during a 3-month period along with conventional treatment with analgesics, or to a control group receiving conventional treatment but no acupuncture.
Patients who did not agree to randomization received acupuncture and were monitored as a third group, said Susanne Jena, M.D., of the Institute for Social Medicine, Charité Medical Center, Berlin.
Three-quarters of the patients were female, and their mean age was 44 years. Of the 3,182 who agreed to randomization, 1,613 were in the acupuncture group and 1,569 were in the control group.
After 3 months of treatment, the frequency of headache days per month decreased from 8.4 days to 4.7 days in the two acupuncture groups, a significantly greater reduction than in the control group (8.1 days per month before treatment and 7.5 days per month post treatment).
The data also were analyzed according to headache type. Patients with migraine had an average of 7 days per month with headache before treatment and 4 days per month with headache after treatment including acupuncture. For those patients with tension-type headache, the average decreased from 10 days per month with headache before treatment to 5 days per month after, she said.
The improvements persisted for the next 3 months, she said.
Among the control group, 70% of patients required concomitant treatment with analgesics, compared with 50% of patients in the acupuncture groups.
The second report, which came from the ARC neck pain study, found similar results among 13,846 patients with chronic neck pain. In this cohort, 68% of whom were women with a mean age of 53 years, 1,753 were randomized to receive acupuncture, 1,698 served as controls, and 10,395 who had declined randomization also received acupuncture.
After 3 months of treatment, improvements on the neck pain disability score were more pronounced in the acupuncture groups than in the control group, said Claudia Becker-Witt, M.D., also with Charité. Scores fell from 56.4 to 39.6 in the acupuncture groups and from 54.5 to 51.2 in the control group, a statistically significant difference.
In both studies, the acupuncture groups also experienced significantly greater improvements in quality of life.
About 8%–9% of patients in both studies experienced side effects from acupuncture; they were not life threatening.
Analyses of cost-effectiveness and overall health benefits are being done, Dr. Becker-Witt said.
Fibromyalgia Pain Responds to Pramipexole
SAN ANTONIO–The dopamine-3 receptor agonist pramipexole significantly improved pain, function, and fatigue in patients with severe, longstanding fibromyalgia, Andrew J. Holman, M.D., said in a late-breaking abstract session at the annual meeting of the American College of Rheumatology.
In a double-blind, randomized, placebo- controlled clinical trial that included 60 patients, pain as measured on a 10-point visual analog scale (VAS) improved by 36%, from a mean score of 7.0 at baseline to 4.5 after 14 weeks of treatment with pramipexole. By contrast, patients receiving placebo experienced only a 9% decrease in pain, from 7.54 to 6.82.
At baseline, all patients had fibromyalgia of at least 6 months' duration and a VAS pain score of at least 5.
Exclusion criteria included untreated sleep apnea, cervical myopathy, uncontrolled psychosis, thyroid disease, and pregnancy. In addition, patients could not have had any prior exposure to dopamine agonists. “I wanted to make this as close to a real-world study as possible, so patients could continue other medications if they were clinically stable and maintained the same dose for 14 weeks,” said Dr. Holman, who is a rheumatologist in private practice in Renton, Wash.
Other drugs taken by the patients included anticonvulsants, antidepressants, anxiolytics, and muscle relaxants. Mean disease duration was 8.6 years, and patients had taken an average of 10 different medications during that time.
On study entrance, 24% of the placebo group and 31% of the pramipexole group were clinically disabled. Moreover, 67% of the placebo group and 44% of the active treatment group were taking daily narcotics for pain relief. Only half were working. The pramipexole dose was titrated up to a target of 4.5 mg /day orally at bedtime.
“In terms of measuring efficacy for pain, we generally look at the number of patients who achieve a greater than 50% reduction in pain,” he said. This outcome was achieved by 42% of patients in the pramipexole arm compared with 14% of those in the placebo arm.
Moderate or greater improvement on the Patients' Global Impression of Change questionnaire was reported by 63% of pramipexole-treated patients, compared with 38% of the placebo patients. Statistically significant improvements were seen on the Fibromyalgia Impact Questionnaire and the fatigue and function scores of the multidimensional Health Assessment Questionnaire.
Secondary end points that showed trends toward improvement with the active treatment include tender point scores, the Hamilton Rating Scale for Depression, and the Beck Anxiety Inventory.
“It was interesting to note that no outcomes favored placebo,” he said.
Pramipexole, used for Parkinson's disease and restless legs syndrome, is thought to inhibit excessive autonomic stimulation and arousal in the mesolimbic area of the hippocampus. It is not a sedating medication. Rather, its effects on arousal may allow normal stage IV sleep. The result is that “we're not making them sleep; we're allowing them to sleep,” Dr. Holman said.
The most pronounced side effect was weight loss, with 40% of the pramipexole group losing between 5 and 35 pounds.
Adverse events associated with pramipexole included increased anxiety, morning somnolence, diarrhea, and vomiting. The hallucinations commonly reported by Parkinson's patients did not occur in this study.
One patient experienced unexpected amnesia that lasted for about 4 hours. She was hospitalized and after 3 days of neural evaluation was discharged without a diagnosis. She wanted to continue in the study and did so without further incident.
One patient in the placebo arm died of causes not related to the study.
Further sleep studies will be needed to more fully elucidate pramipexole's mechanisms of action in the setting of fibromyalgia, he said.
SAN ANTONIO–The dopamine-3 receptor agonist pramipexole significantly improved pain, function, and fatigue in patients with severe, longstanding fibromyalgia, Andrew J. Holman, M.D., said in a late-breaking abstract session at the annual meeting of the American College of Rheumatology.
In a double-blind, randomized, placebo- controlled clinical trial that included 60 patients, pain as measured on a 10-point visual analog scale (VAS) improved by 36%, from a mean score of 7.0 at baseline to 4.5 after 14 weeks of treatment with pramipexole. By contrast, patients receiving placebo experienced only a 9% decrease in pain, from 7.54 to 6.82.
At baseline, all patients had fibromyalgia of at least 6 months' duration and a VAS pain score of at least 5.
Exclusion criteria included untreated sleep apnea, cervical myopathy, uncontrolled psychosis, thyroid disease, and pregnancy. In addition, patients could not have had any prior exposure to dopamine agonists. “I wanted to make this as close to a real-world study as possible, so patients could continue other medications if they were clinically stable and maintained the same dose for 14 weeks,” said Dr. Holman, who is a rheumatologist in private practice in Renton, Wash.
Other drugs taken by the patients included anticonvulsants, antidepressants, anxiolytics, and muscle relaxants. Mean disease duration was 8.6 years, and patients had taken an average of 10 different medications during that time.
On study entrance, 24% of the placebo group and 31% of the pramipexole group were clinically disabled. Moreover, 67% of the placebo group and 44% of the active treatment group were taking daily narcotics for pain relief. Only half were working. The pramipexole dose was titrated up to a target of 4.5 mg /day orally at bedtime.
“In terms of measuring efficacy for pain, we generally look at the number of patients who achieve a greater than 50% reduction in pain,” he said. This outcome was achieved by 42% of patients in the pramipexole arm compared with 14% of those in the placebo arm.
Moderate or greater improvement on the Patients' Global Impression of Change questionnaire was reported by 63% of pramipexole-treated patients, compared with 38% of the placebo patients. Statistically significant improvements were seen on the Fibromyalgia Impact Questionnaire and the fatigue and function scores of the multidimensional Health Assessment Questionnaire.
Secondary end points that showed trends toward improvement with the active treatment include tender point scores, the Hamilton Rating Scale for Depression, and the Beck Anxiety Inventory.
“It was interesting to note that no outcomes favored placebo,” he said.
Pramipexole, used for Parkinson's disease and restless legs syndrome, is thought to inhibit excessive autonomic stimulation and arousal in the mesolimbic area of the hippocampus. It is not a sedating medication. Rather, its effects on arousal may allow normal stage IV sleep. The result is that “we're not making them sleep; we're allowing them to sleep,” Dr. Holman said.
The most pronounced side effect was weight loss, with 40% of the pramipexole group losing between 5 and 35 pounds.
Adverse events associated with pramipexole included increased anxiety, morning somnolence, diarrhea, and vomiting. The hallucinations commonly reported by Parkinson's patients did not occur in this study.
One patient experienced unexpected amnesia that lasted for about 4 hours. She was hospitalized and after 3 days of neural evaluation was discharged without a diagnosis. She wanted to continue in the study and did so without further incident.
One patient in the placebo arm died of causes not related to the study.
Further sleep studies will be needed to more fully elucidate pramipexole's mechanisms of action in the setting of fibromyalgia, he said.
SAN ANTONIO–The dopamine-3 receptor agonist pramipexole significantly improved pain, function, and fatigue in patients with severe, longstanding fibromyalgia, Andrew J. Holman, M.D., said in a late-breaking abstract session at the annual meeting of the American College of Rheumatology.
In a double-blind, randomized, placebo- controlled clinical trial that included 60 patients, pain as measured on a 10-point visual analog scale (VAS) improved by 36%, from a mean score of 7.0 at baseline to 4.5 after 14 weeks of treatment with pramipexole. By contrast, patients receiving placebo experienced only a 9% decrease in pain, from 7.54 to 6.82.
At baseline, all patients had fibromyalgia of at least 6 months' duration and a VAS pain score of at least 5.
Exclusion criteria included untreated sleep apnea, cervical myopathy, uncontrolled psychosis, thyroid disease, and pregnancy. In addition, patients could not have had any prior exposure to dopamine agonists. “I wanted to make this as close to a real-world study as possible, so patients could continue other medications if they were clinically stable and maintained the same dose for 14 weeks,” said Dr. Holman, who is a rheumatologist in private practice in Renton, Wash.
Other drugs taken by the patients included anticonvulsants, antidepressants, anxiolytics, and muscle relaxants. Mean disease duration was 8.6 years, and patients had taken an average of 10 different medications during that time.
On study entrance, 24% of the placebo group and 31% of the pramipexole group were clinically disabled. Moreover, 67% of the placebo group and 44% of the active treatment group were taking daily narcotics for pain relief. Only half were working. The pramipexole dose was titrated up to a target of 4.5 mg /day orally at bedtime.
“In terms of measuring efficacy for pain, we generally look at the number of patients who achieve a greater than 50% reduction in pain,” he said. This outcome was achieved by 42% of patients in the pramipexole arm compared with 14% of those in the placebo arm.
Moderate or greater improvement on the Patients' Global Impression of Change questionnaire was reported by 63% of pramipexole-treated patients, compared with 38% of the placebo patients. Statistically significant improvements were seen on the Fibromyalgia Impact Questionnaire and the fatigue and function scores of the multidimensional Health Assessment Questionnaire.
Secondary end points that showed trends toward improvement with the active treatment include tender point scores, the Hamilton Rating Scale for Depression, and the Beck Anxiety Inventory.
“It was interesting to note that no outcomes favored placebo,” he said.
Pramipexole, used for Parkinson's disease and restless legs syndrome, is thought to inhibit excessive autonomic stimulation and arousal in the mesolimbic area of the hippocampus. It is not a sedating medication. Rather, its effects on arousal may allow normal stage IV sleep. The result is that “we're not making them sleep; we're allowing them to sleep,” Dr. Holman said.
The most pronounced side effect was weight loss, with 40% of the pramipexole group losing between 5 and 35 pounds.
Adverse events associated with pramipexole included increased anxiety, morning somnolence, diarrhea, and vomiting. The hallucinations commonly reported by Parkinson's patients did not occur in this study.
One patient experienced unexpected amnesia that lasted for about 4 hours. She was hospitalized and after 3 days of neural evaluation was discharged without a diagnosis. She wanted to continue in the study and did so without further incident.
One patient in the placebo arm died of causes not related to the study.
Further sleep studies will be needed to more fully elucidate pramipexole's mechanisms of action in the setting of fibromyalgia, he said.
Study Design May Miss Hypnotherapy's Benefits
EXETER, ENGLAND — The benefits of complementary therapies such as hypnotherapy are likely to be underestimated when they are evaluated using conventional clinical trial designs and outcome measures, according to Lesley M. Roberts, M.D., of the department of primary care, University of Birmingham (England).
Gut-directed hypnotherapy has been found effective in more than a dozen studies during the past 20 years. But a clinical trial in which 81 patients with irritable bowel syndrome (IBS) were randomized to hypnotherapy or usual care by a primary care physician found little difference between the two.
Was this a case of “right intervention, wrong outcome?” Dr. Roberts asked at a symposium on alternative and complementary therapies that was sponsored by the universities of Exeter and Plymouth. “My background is in conventional medicine, so we chose conventional tools for the study—symptom scores and [an] IBS quality of life tool,” she explained.
Such disease-specific tools are allegedly more sensitive than generic tools for evaluating conventional therapies.
Patients in the study had gastroenterologist-confirmed IBS of 6 weeks' duration or longer and had failed at least one conventional treatment. They were evaluated at baseline and at 3, 6, and 12 months.
Both groups improved during the trial. Symptom scores, pain, and diarrhea were significantly superior in the hypnotherapy group at 3 months, but the difference was not maintained over time.
There were no between-group differences at any time point for constipation or quality of life.
Yet “when we asked patients in the hypnotherapy group about their experiences, 81% reported definite improvement, 55% reported improvement greater than they had anticipated, and 91% would recommend gut-directed hypnotherapy to their friends,” Dr. Roberts said. “Did our study miss some important benefits? Patients were saying they felt better. The treatment was very helpful for mental well being, and it gave them control—all generic quality of life concerns. Yet we didn't pick up any quality of life benefit using the IBS-specific quality of life tool.”
Perhaps complementary and alternative medicine research should use more generic outcome measures, such as the subjective assessment questionnaire used in the Manchester protocol. “I think the benefit of hypnotherapy is that patients are better able to cope, not that they necessarily have fewer symptoms. They feel empowered,” she said.
“If I were to do this again I would do lots of pilot work, qualitative work, and I definitely would use generic rather than disease-specific outcome measures because I think that is the mechanism by which a lot of complementary therapies work,” Dr. Roberts said.
EXETER, ENGLAND — The benefits of complementary therapies such as hypnotherapy are likely to be underestimated when they are evaluated using conventional clinical trial designs and outcome measures, according to Lesley M. Roberts, M.D., of the department of primary care, University of Birmingham (England).
Gut-directed hypnotherapy has been found effective in more than a dozen studies during the past 20 years. But a clinical trial in which 81 patients with irritable bowel syndrome (IBS) were randomized to hypnotherapy or usual care by a primary care physician found little difference between the two.
Was this a case of “right intervention, wrong outcome?” Dr. Roberts asked at a symposium on alternative and complementary therapies that was sponsored by the universities of Exeter and Plymouth. “My background is in conventional medicine, so we chose conventional tools for the study—symptom scores and [an] IBS quality of life tool,” she explained.
Such disease-specific tools are allegedly more sensitive than generic tools for evaluating conventional therapies.
Patients in the study had gastroenterologist-confirmed IBS of 6 weeks' duration or longer and had failed at least one conventional treatment. They were evaluated at baseline and at 3, 6, and 12 months.
Both groups improved during the trial. Symptom scores, pain, and diarrhea were significantly superior in the hypnotherapy group at 3 months, but the difference was not maintained over time.
There were no between-group differences at any time point for constipation or quality of life.
Yet “when we asked patients in the hypnotherapy group about their experiences, 81% reported definite improvement, 55% reported improvement greater than they had anticipated, and 91% would recommend gut-directed hypnotherapy to their friends,” Dr. Roberts said. “Did our study miss some important benefits? Patients were saying they felt better. The treatment was very helpful for mental well being, and it gave them control—all generic quality of life concerns. Yet we didn't pick up any quality of life benefit using the IBS-specific quality of life tool.”
Perhaps complementary and alternative medicine research should use more generic outcome measures, such as the subjective assessment questionnaire used in the Manchester protocol. “I think the benefit of hypnotherapy is that patients are better able to cope, not that they necessarily have fewer symptoms. They feel empowered,” she said.
“If I were to do this again I would do lots of pilot work, qualitative work, and I definitely would use generic rather than disease-specific outcome measures because I think that is the mechanism by which a lot of complementary therapies work,” Dr. Roberts said.
EXETER, ENGLAND — The benefits of complementary therapies such as hypnotherapy are likely to be underestimated when they are evaluated using conventional clinical trial designs and outcome measures, according to Lesley M. Roberts, M.D., of the department of primary care, University of Birmingham (England).
Gut-directed hypnotherapy has been found effective in more than a dozen studies during the past 20 years. But a clinical trial in which 81 patients with irritable bowel syndrome (IBS) were randomized to hypnotherapy or usual care by a primary care physician found little difference between the two.
Was this a case of “right intervention, wrong outcome?” Dr. Roberts asked at a symposium on alternative and complementary therapies that was sponsored by the universities of Exeter and Plymouth. “My background is in conventional medicine, so we chose conventional tools for the study—symptom scores and [an] IBS quality of life tool,” she explained.
Such disease-specific tools are allegedly more sensitive than generic tools for evaluating conventional therapies.
Patients in the study had gastroenterologist-confirmed IBS of 6 weeks' duration or longer and had failed at least one conventional treatment. They were evaluated at baseline and at 3, 6, and 12 months.
Both groups improved during the trial. Symptom scores, pain, and diarrhea were significantly superior in the hypnotherapy group at 3 months, but the difference was not maintained over time.
There were no between-group differences at any time point for constipation or quality of life.
Yet “when we asked patients in the hypnotherapy group about their experiences, 81% reported definite improvement, 55% reported improvement greater than they had anticipated, and 91% would recommend gut-directed hypnotherapy to their friends,” Dr. Roberts said. “Did our study miss some important benefits? Patients were saying they felt better. The treatment was very helpful for mental well being, and it gave them control—all generic quality of life concerns. Yet we didn't pick up any quality of life benefit using the IBS-specific quality of life tool.”
Perhaps complementary and alternative medicine research should use more generic outcome measures, such as the subjective assessment questionnaire used in the Manchester protocol. “I think the benefit of hypnotherapy is that patients are better able to cope, not that they necessarily have fewer symptoms. They feel empowered,” she said.
“If I were to do this again I would do lots of pilot work, qualitative work, and I definitely would use generic rather than disease-specific outcome measures because I think that is the mechanism by which a lot of complementary therapies work,” Dr. Roberts said.
PTH Prevents First Fractures in Early Osteoporosis
SAN ANTONIO — Intact human recombinant parathyroid hormone prevented both recurrent and first fractures in a multinational, randomized, placebo-controlled study of postmenopausal women with osteoporosis, Mark P. Ettinger, M.D., said at the annual meeting of the American College of Rheumatology.
Previous studies have shown that the parathyroid hormone (PTH) analog teriperatide can prevent fractures in patients with advanced disease who already have had a fracture. The Treatment of Osteoporosis With PTH (TOP) study was the first to demonstrate the prevention of first fractures in patients with earlier disease, Dr. Ettinger said.
“This is extremely important, because the presence of any existing fracture greatly increases the risk of subsequent fractures,” he said.
The TOP study included 2,532 women whose mean age was 64.4 years and whose mean spine, total hip, and femoral neck bone mineral density (BMD) T-scores were -3.0, -1.9, and -2.2, respectively.
The study population was very different from other osteoporosis treatment cohorts, in that the patients were younger, and only 19% already had fractures. In previous PTH phase II and teriperatide phase III trials, fracture prevalence ranged from 37% to 100%, he said.
Patients were randomized to 100 mcg subcutaneous PTH daily or placebo. All patients also took 700 mg calcium and 400 U vitamin D each day.
A total of 1,737 patients—72% and 65% of the placebo and PTH groups, respectively—completed the 18-month study.
At study completion, the vertebral fracture incidence was 3.33% in the placebo group and 1.14% in the PTH group, which represented a relative fracture risk reduction of 66%, said Dr. Ettinger, medical director emeritus of Radiant Research, Stuart, Fla.
In a per-protocol analysis, patients who had a fracture before entering the study had a 69% relative fracture risk reduction; those without a previous fracture had a risk reduction of 63%.
At month 18 the mean spine, total hip, and femoral neck BMD had increased by 7.2%, 2.2%, and 2.5%, respectively, in the PTH group relative to the placebo group, he said. This included patients allowed to take PTH on a less-than-daily schedule.
About 9% of the PTH group withdrew because of headache, dizziness, nausea, or vomiting, or elevated serum or urine calcium levels. Overall, 16% of PTH patients and 12% of placebo patients withdrew during the course of the study. There were two deaths in the placebo group and one in the PTH group; this was judged to be unrelated to treatment.
“The results of the TOP study may change our treatment paradigm somewhat and shift our target population to younger patients or those with less severe disease someday,” Dr. Ettinger told this newspaper. “Might we even dare say the word 'cure,' in that very large increases in bone density are possible in relatively short periods of time?” he asked.
The recommended use for anabolic agents such as PTH and its analogs is to give them for 18-24 months, after which time an antiresorptive agent, such as a bisphosphonate, is given to preserve the gains, continue improvement of bone density and quality, and continue mineralization.
Bisphosphonates are not given concurrently with PTH because they tend to blunt the response to PTH, at least for the first 6 months, he said. More information is needed as to how much blunting might occur with less potent antiresorptives, such as estrogen or raloxifene.
Dr. Ettinger disclosed that he received research grants and consulting fees from many pharmaceutical companies including NPS Pharmaceuticals, the Salt Lake City-based manufacturer of PTH. An expanded new drug application package for the company's proprietary formulation, Preos, is planned for February 2005, according to the NPS Web site.
SAN ANTONIO — Intact human recombinant parathyroid hormone prevented both recurrent and first fractures in a multinational, randomized, placebo-controlled study of postmenopausal women with osteoporosis, Mark P. Ettinger, M.D., said at the annual meeting of the American College of Rheumatology.
Previous studies have shown that the parathyroid hormone (PTH) analog teriperatide can prevent fractures in patients with advanced disease who already have had a fracture. The Treatment of Osteoporosis With PTH (TOP) study was the first to demonstrate the prevention of first fractures in patients with earlier disease, Dr. Ettinger said.
“This is extremely important, because the presence of any existing fracture greatly increases the risk of subsequent fractures,” he said.
The TOP study included 2,532 women whose mean age was 64.4 years and whose mean spine, total hip, and femoral neck bone mineral density (BMD) T-scores were -3.0, -1.9, and -2.2, respectively.
The study population was very different from other osteoporosis treatment cohorts, in that the patients were younger, and only 19% already had fractures. In previous PTH phase II and teriperatide phase III trials, fracture prevalence ranged from 37% to 100%, he said.
Patients were randomized to 100 mcg subcutaneous PTH daily or placebo. All patients also took 700 mg calcium and 400 U vitamin D each day.
A total of 1,737 patients—72% and 65% of the placebo and PTH groups, respectively—completed the 18-month study.
At study completion, the vertebral fracture incidence was 3.33% in the placebo group and 1.14% in the PTH group, which represented a relative fracture risk reduction of 66%, said Dr. Ettinger, medical director emeritus of Radiant Research, Stuart, Fla.
In a per-protocol analysis, patients who had a fracture before entering the study had a 69% relative fracture risk reduction; those without a previous fracture had a risk reduction of 63%.
At month 18 the mean spine, total hip, and femoral neck BMD had increased by 7.2%, 2.2%, and 2.5%, respectively, in the PTH group relative to the placebo group, he said. This included patients allowed to take PTH on a less-than-daily schedule.
About 9% of the PTH group withdrew because of headache, dizziness, nausea, or vomiting, or elevated serum or urine calcium levels. Overall, 16% of PTH patients and 12% of placebo patients withdrew during the course of the study. There were two deaths in the placebo group and one in the PTH group; this was judged to be unrelated to treatment.
“The results of the TOP study may change our treatment paradigm somewhat and shift our target population to younger patients or those with less severe disease someday,” Dr. Ettinger told this newspaper. “Might we even dare say the word 'cure,' in that very large increases in bone density are possible in relatively short periods of time?” he asked.
The recommended use for anabolic agents such as PTH and its analogs is to give them for 18-24 months, after which time an antiresorptive agent, such as a bisphosphonate, is given to preserve the gains, continue improvement of bone density and quality, and continue mineralization.
Bisphosphonates are not given concurrently with PTH because they tend to blunt the response to PTH, at least for the first 6 months, he said. More information is needed as to how much blunting might occur with less potent antiresorptives, such as estrogen or raloxifene.
Dr. Ettinger disclosed that he received research grants and consulting fees from many pharmaceutical companies including NPS Pharmaceuticals, the Salt Lake City-based manufacturer of PTH. An expanded new drug application package for the company's proprietary formulation, Preos, is planned for February 2005, according to the NPS Web site.
SAN ANTONIO — Intact human recombinant parathyroid hormone prevented both recurrent and first fractures in a multinational, randomized, placebo-controlled study of postmenopausal women with osteoporosis, Mark P. Ettinger, M.D., said at the annual meeting of the American College of Rheumatology.
Previous studies have shown that the parathyroid hormone (PTH) analog teriperatide can prevent fractures in patients with advanced disease who already have had a fracture. The Treatment of Osteoporosis With PTH (TOP) study was the first to demonstrate the prevention of first fractures in patients with earlier disease, Dr. Ettinger said.
“This is extremely important, because the presence of any existing fracture greatly increases the risk of subsequent fractures,” he said.
The TOP study included 2,532 women whose mean age was 64.4 years and whose mean spine, total hip, and femoral neck bone mineral density (BMD) T-scores were -3.0, -1.9, and -2.2, respectively.
The study population was very different from other osteoporosis treatment cohorts, in that the patients were younger, and only 19% already had fractures. In previous PTH phase II and teriperatide phase III trials, fracture prevalence ranged from 37% to 100%, he said.
Patients were randomized to 100 mcg subcutaneous PTH daily or placebo. All patients also took 700 mg calcium and 400 U vitamin D each day.
A total of 1,737 patients—72% and 65% of the placebo and PTH groups, respectively—completed the 18-month study.
At study completion, the vertebral fracture incidence was 3.33% in the placebo group and 1.14% in the PTH group, which represented a relative fracture risk reduction of 66%, said Dr. Ettinger, medical director emeritus of Radiant Research, Stuart, Fla.
In a per-protocol analysis, patients who had a fracture before entering the study had a 69% relative fracture risk reduction; those without a previous fracture had a risk reduction of 63%.
At month 18 the mean spine, total hip, and femoral neck BMD had increased by 7.2%, 2.2%, and 2.5%, respectively, in the PTH group relative to the placebo group, he said. This included patients allowed to take PTH on a less-than-daily schedule.
About 9% of the PTH group withdrew because of headache, dizziness, nausea, or vomiting, or elevated serum or urine calcium levels. Overall, 16% of PTH patients and 12% of placebo patients withdrew during the course of the study. There were two deaths in the placebo group and one in the PTH group; this was judged to be unrelated to treatment.
“The results of the TOP study may change our treatment paradigm somewhat and shift our target population to younger patients or those with less severe disease someday,” Dr. Ettinger told this newspaper. “Might we even dare say the word 'cure,' in that very large increases in bone density are possible in relatively short periods of time?” he asked.
The recommended use for anabolic agents such as PTH and its analogs is to give them for 18-24 months, after which time an antiresorptive agent, such as a bisphosphonate, is given to preserve the gains, continue improvement of bone density and quality, and continue mineralization.
Bisphosphonates are not given concurrently with PTH because they tend to blunt the response to PTH, at least for the first 6 months, he said. More information is needed as to how much blunting might occur with less potent antiresorptives, such as estrogen or raloxifene.
Dr. Ettinger disclosed that he received research grants and consulting fees from many pharmaceutical companies including NPS Pharmaceuticals, the Salt Lake City-based manufacturer of PTH. An expanded new drug application package for the company's proprietary formulation, Preos, is planned for February 2005, according to the NPS Web site.
Acupuncture Improves Knee OA in Phase III Study
SAN ANTONIO — Acupuncture has shown itself to be an effective adjunct in the treatment of osteoarthritis of the knee in a large phase III study funded by the National Center for Complementary and Alternative Medicine.
In a randomized clinical trial that compared traditional Chinese acupuncture with sham acupuncture or an educational program, statistically significant improvements were seen in pain and function with true acupuncture, Marc C. Hochberg, M.D., said at the annual meeting of the American College of Rheumatology.
The study included 570 patients with symptomatic knee osteoarthritis (OA), defined as moderate to severe pain on a 5-point Likert scale despite therapy with analgesics and anti-inflammatory agents.
The mean age of the patients was 65.5 years, 69% were white, and 64% were women.
True acupuncture intervention consisted of insertion of needles at 5 local points and 4 points distal to the knee, said Dr. Hochberg, professor of medicine, University of Maryland, Baltimore. The acupuncture points were determined according to the precepts of traditional Chinese medicine, which classifies all types of arthritis as “Bi syndrome.”
Additionally, low frequency electrical stimulation was applied at a single point in the infrapatellar area.
Patients received acupuncture treatments twice a week for 8 weeks, then weekly for 2 weeks, every other week for 4 weeks, and monthly for 3 months, for a total of 25 treatments over 26 weeks.
The validated sham acupuncture intervention consisted of the tapping of needles, without insertion, at the same acupuncture points, insertion of needles at 2 nonacupuncture points on the abdomen, and a mock TENS unit was applied to the infrapatellar point.
Patients randomized to the education group underwent the Arthritis Self-Help course attending 2 hours of classes weekly for 12 weeks and had monthly telephone calls for the duration of the study.
The primary outcome measures were the pain and function subscales of the Western Ontario and McMasters Universities (WOMAC) OA index. Ranges for the pain subscale are 0- 20, while those for the function subscale are 0–68.
By week 26 significant differences in pain and function were seen for the true acupuncture group compared to the sham acupuncture group. (See box.)
On secondary outcome measures, statistically significant differences were seen on patient global assessment between the true and sham acupuncture groups, though not on the SF-36 subscale or the 6-minute walk test, he said.
“The effect size is rather small, at about .25,” Dr. Hochberg said. This is similar to that reported for intra-articular injections of hyaluronic acid (JAMA 2003; 290:3115–21).
Adverse events were uncommon and did not differ by treatment group. No adverse events were attributed to acupuncture.
This “is clearly the most definitive study to date looking at acupuncture for arthritis and it supports the suggestion from previous, smaller and less well-designed trials that acupuncture can have adjunctive benefit in the management of osteoarthritis pain,” Sharon Kolasinski, M.D., noted in an interview.
“Certainly, this study strengthens the argument that it is reasonable to consider acupuncture among the adjunctive therapies available to us for management of osteoarthritis pain,” said Dr. Kolasinski, chief of clinical services in the Department of Rheumatology at the University of Pennsylvania. Although the effect size was small, Dr. Kolasinski emphasized that the patients were already being treated by standard interventions and still had inadequate control of symptoms.
“Despite the fact that it's a small effect size, one must recognize that this is added onto background therapy, which in the majority of these patients included NSAIDs with or without additional analgesics,” Dr. Hochberg added.
A repeated measures analysis was conducted in order to “look at the pattern of response, and we anticipated that we would see a similar early response to sham and traditional acupuncture, corresponding to the placebo effect, and that the curves would then separate out over time,” he said.
Dr. Kolasinski added that a second NIH-funded trial currently being conducted at the University of Pennsylvania comparing physical therapy to physical therapy plus acupuncture for osteoarthritis of the knee “should give us additional information about the optimal use of acupuncture for osteoarthritis.
SAN ANTONIO — Acupuncture has shown itself to be an effective adjunct in the treatment of osteoarthritis of the knee in a large phase III study funded by the National Center for Complementary and Alternative Medicine.
In a randomized clinical trial that compared traditional Chinese acupuncture with sham acupuncture or an educational program, statistically significant improvements were seen in pain and function with true acupuncture, Marc C. Hochberg, M.D., said at the annual meeting of the American College of Rheumatology.
The study included 570 patients with symptomatic knee osteoarthritis (OA), defined as moderate to severe pain on a 5-point Likert scale despite therapy with analgesics and anti-inflammatory agents.
The mean age of the patients was 65.5 years, 69% were white, and 64% were women.
True acupuncture intervention consisted of insertion of needles at 5 local points and 4 points distal to the knee, said Dr. Hochberg, professor of medicine, University of Maryland, Baltimore. The acupuncture points were determined according to the precepts of traditional Chinese medicine, which classifies all types of arthritis as “Bi syndrome.”
Additionally, low frequency electrical stimulation was applied at a single point in the infrapatellar area.
Patients received acupuncture treatments twice a week for 8 weeks, then weekly for 2 weeks, every other week for 4 weeks, and monthly for 3 months, for a total of 25 treatments over 26 weeks.
The validated sham acupuncture intervention consisted of the tapping of needles, without insertion, at the same acupuncture points, insertion of needles at 2 nonacupuncture points on the abdomen, and a mock TENS unit was applied to the infrapatellar point.
Patients randomized to the education group underwent the Arthritis Self-Help course attending 2 hours of classes weekly for 12 weeks and had monthly telephone calls for the duration of the study.
The primary outcome measures were the pain and function subscales of the Western Ontario and McMasters Universities (WOMAC) OA index. Ranges for the pain subscale are 0- 20, while those for the function subscale are 0–68.
By week 26 significant differences in pain and function were seen for the true acupuncture group compared to the sham acupuncture group. (See box.)
On secondary outcome measures, statistically significant differences were seen on patient global assessment between the true and sham acupuncture groups, though not on the SF-36 subscale or the 6-minute walk test, he said.
“The effect size is rather small, at about .25,” Dr. Hochberg said. This is similar to that reported for intra-articular injections of hyaluronic acid (JAMA 2003; 290:3115–21).
Adverse events were uncommon and did not differ by treatment group. No adverse events were attributed to acupuncture.
This “is clearly the most definitive study to date looking at acupuncture for arthritis and it supports the suggestion from previous, smaller and less well-designed trials that acupuncture can have adjunctive benefit in the management of osteoarthritis pain,” Sharon Kolasinski, M.D., noted in an interview.
“Certainly, this study strengthens the argument that it is reasonable to consider acupuncture among the adjunctive therapies available to us for management of osteoarthritis pain,” said Dr. Kolasinski, chief of clinical services in the Department of Rheumatology at the University of Pennsylvania. Although the effect size was small, Dr. Kolasinski emphasized that the patients were already being treated by standard interventions and still had inadequate control of symptoms.
“Despite the fact that it's a small effect size, one must recognize that this is added onto background therapy, which in the majority of these patients included NSAIDs with or without additional analgesics,” Dr. Hochberg added.
A repeated measures analysis was conducted in order to “look at the pattern of response, and we anticipated that we would see a similar early response to sham and traditional acupuncture, corresponding to the placebo effect, and that the curves would then separate out over time,” he said.
Dr. Kolasinski added that a second NIH-funded trial currently being conducted at the University of Pennsylvania comparing physical therapy to physical therapy plus acupuncture for osteoarthritis of the knee “should give us additional information about the optimal use of acupuncture for osteoarthritis.
SAN ANTONIO — Acupuncture has shown itself to be an effective adjunct in the treatment of osteoarthritis of the knee in a large phase III study funded by the National Center for Complementary and Alternative Medicine.
In a randomized clinical trial that compared traditional Chinese acupuncture with sham acupuncture or an educational program, statistically significant improvements were seen in pain and function with true acupuncture, Marc C. Hochberg, M.D., said at the annual meeting of the American College of Rheumatology.
The study included 570 patients with symptomatic knee osteoarthritis (OA), defined as moderate to severe pain on a 5-point Likert scale despite therapy with analgesics and anti-inflammatory agents.
The mean age of the patients was 65.5 years, 69% were white, and 64% were women.
True acupuncture intervention consisted of insertion of needles at 5 local points and 4 points distal to the knee, said Dr. Hochberg, professor of medicine, University of Maryland, Baltimore. The acupuncture points were determined according to the precepts of traditional Chinese medicine, which classifies all types of arthritis as “Bi syndrome.”
Additionally, low frequency electrical stimulation was applied at a single point in the infrapatellar area.
Patients received acupuncture treatments twice a week for 8 weeks, then weekly for 2 weeks, every other week for 4 weeks, and monthly for 3 months, for a total of 25 treatments over 26 weeks.
The validated sham acupuncture intervention consisted of the tapping of needles, without insertion, at the same acupuncture points, insertion of needles at 2 nonacupuncture points on the abdomen, and a mock TENS unit was applied to the infrapatellar point.
Patients randomized to the education group underwent the Arthritis Self-Help course attending 2 hours of classes weekly for 12 weeks and had monthly telephone calls for the duration of the study.
The primary outcome measures were the pain and function subscales of the Western Ontario and McMasters Universities (WOMAC) OA index. Ranges for the pain subscale are 0- 20, while those for the function subscale are 0–68.
By week 26 significant differences in pain and function were seen for the true acupuncture group compared to the sham acupuncture group. (See box.)
On secondary outcome measures, statistically significant differences were seen on patient global assessment between the true and sham acupuncture groups, though not on the SF-36 subscale or the 6-minute walk test, he said.
“The effect size is rather small, at about .25,” Dr. Hochberg said. This is similar to that reported for intra-articular injections of hyaluronic acid (JAMA 2003; 290:3115–21).
Adverse events were uncommon and did not differ by treatment group. No adverse events were attributed to acupuncture.
This “is clearly the most definitive study to date looking at acupuncture for arthritis and it supports the suggestion from previous, smaller and less well-designed trials that acupuncture can have adjunctive benefit in the management of osteoarthritis pain,” Sharon Kolasinski, M.D., noted in an interview.
“Certainly, this study strengthens the argument that it is reasonable to consider acupuncture among the adjunctive therapies available to us for management of osteoarthritis pain,” said Dr. Kolasinski, chief of clinical services in the Department of Rheumatology at the University of Pennsylvania. Although the effect size was small, Dr. Kolasinski emphasized that the patients were already being treated by standard interventions and still had inadequate control of symptoms.
“Despite the fact that it's a small effect size, one must recognize that this is added onto background therapy, which in the majority of these patients included NSAIDs with or without additional analgesics,” Dr. Hochberg added.
A repeated measures analysis was conducted in order to “look at the pattern of response, and we anticipated that we would see a similar early response to sham and traditional acupuncture, corresponding to the placebo effect, and that the curves would then separate out over time,” he said.
Dr. Kolasinski added that a second NIH-funded trial currently being conducted at the University of Pennsylvania comparing physical therapy to physical therapy plus acupuncture for osteoarthritis of the knee “should give us additional information about the optimal use of acupuncture for osteoarthritis.
Biologics Don't Drive Up Risk of Uveitis in JIA
SAN ANTONIO — Certain children with juvenile idiopathic arthritis are at risk for developing uveitis, but treatment with biologic agents does not increase this risk, Rotraud K. Saurenmann, M.D., said at the annual meeting of the American College of Rheumatology.
Tumor necrosis factor (TNF)-α therapy has been used successfully to treat pediatric uveitis, but concern has arisen because there have been reports of cases of new-onset JIA-associated uveitis occurring during treatment with these drugs.
In an effort to clarify a possible link between anti-TNF-α treatment and uveitis, Dr. Saurenmann and her colleagues at the Hospital for Sick Children, Toronto, performed a retrospective chart review of all children with a diagnosis of JIA treated at her center between 1996 and 2003.
Among the 1,109 patients identified, 145 had developed uveitis sometime in the course of their disease and so were considered to be at risk for subsequent episodes. Among those with the ocular complication, 87 had been treated with anti-TNF-α therapy.
However, in 17 cases, the uveitis predated the anti-TNF-α treatment, so a causal effect was ruled out.
In the 70 remaining patients treated with anti-TNF-α therapy, there were 2 cases of new-onset uveitis, both in patients receiving etanercept.
One of the patients with new-onset uveitis had a 4-year history of psoriatic arthritis, and the other patient had had oligoarticular JIA for 6.4 years.
Cox regression analysis was carried out for these 70 patients, using new-onset uveitis as the primary end point and anti-TNF-α as a time-dependent variable.
There was no statistically significant difference in risk of uveitis between patients with and without a history of taking anti-TNF-α therapy, Dr. Saurenmann noted during her presenation.
And when the possible association between uveitis and biologic therapy was analyzed according to JIA subtypes, those with oligoarticular JIA had an increased risk, as did those who were antinuclear antibody (ANA) positive and rheumatoid factor (RF) negative, she said.
Patients who developed JIA at a young age also were at increased risk, and the ocular complication typically occurred early in the course of disease.
Children with psoriatic arthritis also are at risk, but those with RF positive and systemic onset JIA are not.
“So we asked ourselves which at-risk patients would be eligible for anti-TNF-α treatment, and that would be those with oligoarticular disease; those with polyarticular, RF-negative disease; and those with psoriatic JIA,” she said.
A total of 434 patients fell into those groups; 45 of these had received anti-TNF-α treatment.
But once again Cox regression analysis found no difference in risk between those with and without anti-TNF-α treatment, she said.
“We concluded that anti-TNF-α therapy does not alter the risk for the development of new onset uveitis in children with JIA,” she said.
SAN ANTONIO — Certain children with juvenile idiopathic arthritis are at risk for developing uveitis, but treatment with biologic agents does not increase this risk, Rotraud K. Saurenmann, M.D., said at the annual meeting of the American College of Rheumatology.
Tumor necrosis factor (TNF)-α therapy has been used successfully to treat pediatric uveitis, but concern has arisen because there have been reports of cases of new-onset JIA-associated uveitis occurring during treatment with these drugs.
In an effort to clarify a possible link between anti-TNF-α treatment and uveitis, Dr. Saurenmann and her colleagues at the Hospital for Sick Children, Toronto, performed a retrospective chart review of all children with a diagnosis of JIA treated at her center between 1996 and 2003.
Among the 1,109 patients identified, 145 had developed uveitis sometime in the course of their disease and so were considered to be at risk for subsequent episodes. Among those with the ocular complication, 87 had been treated with anti-TNF-α therapy.
However, in 17 cases, the uveitis predated the anti-TNF-α treatment, so a causal effect was ruled out.
In the 70 remaining patients treated with anti-TNF-α therapy, there were 2 cases of new-onset uveitis, both in patients receiving etanercept.
One of the patients with new-onset uveitis had a 4-year history of psoriatic arthritis, and the other patient had had oligoarticular JIA for 6.4 years.
Cox regression analysis was carried out for these 70 patients, using new-onset uveitis as the primary end point and anti-TNF-α as a time-dependent variable.
There was no statistically significant difference in risk of uveitis between patients with and without a history of taking anti-TNF-α therapy, Dr. Saurenmann noted during her presenation.
And when the possible association between uveitis and biologic therapy was analyzed according to JIA subtypes, those with oligoarticular JIA had an increased risk, as did those who were antinuclear antibody (ANA) positive and rheumatoid factor (RF) negative, she said.
Patients who developed JIA at a young age also were at increased risk, and the ocular complication typically occurred early in the course of disease.
Children with psoriatic arthritis also are at risk, but those with RF positive and systemic onset JIA are not.
“So we asked ourselves which at-risk patients would be eligible for anti-TNF-α treatment, and that would be those with oligoarticular disease; those with polyarticular, RF-negative disease; and those with psoriatic JIA,” she said.
A total of 434 patients fell into those groups; 45 of these had received anti-TNF-α treatment.
But once again Cox regression analysis found no difference in risk between those with and without anti-TNF-α treatment, she said.
“We concluded that anti-TNF-α therapy does not alter the risk for the development of new onset uveitis in children with JIA,” she said.
SAN ANTONIO — Certain children with juvenile idiopathic arthritis are at risk for developing uveitis, but treatment with biologic agents does not increase this risk, Rotraud K. Saurenmann, M.D., said at the annual meeting of the American College of Rheumatology.
Tumor necrosis factor (TNF)-α therapy has been used successfully to treat pediatric uveitis, but concern has arisen because there have been reports of cases of new-onset JIA-associated uveitis occurring during treatment with these drugs.
In an effort to clarify a possible link between anti-TNF-α treatment and uveitis, Dr. Saurenmann and her colleagues at the Hospital for Sick Children, Toronto, performed a retrospective chart review of all children with a diagnosis of JIA treated at her center between 1996 and 2003.
Among the 1,109 patients identified, 145 had developed uveitis sometime in the course of their disease and so were considered to be at risk for subsequent episodes. Among those with the ocular complication, 87 had been treated with anti-TNF-α therapy.
However, in 17 cases, the uveitis predated the anti-TNF-α treatment, so a causal effect was ruled out.
In the 70 remaining patients treated with anti-TNF-α therapy, there were 2 cases of new-onset uveitis, both in patients receiving etanercept.
One of the patients with new-onset uveitis had a 4-year history of psoriatic arthritis, and the other patient had had oligoarticular JIA for 6.4 years.
Cox regression analysis was carried out for these 70 patients, using new-onset uveitis as the primary end point and anti-TNF-α as a time-dependent variable.
There was no statistically significant difference in risk of uveitis between patients with and without a history of taking anti-TNF-α therapy, Dr. Saurenmann noted during her presenation.
And when the possible association between uveitis and biologic therapy was analyzed according to JIA subtypes, those with oligoarticular JIA had an increased risk, as did those who were antinuclear antibody (ANA) positive and rheumatoid factor (RF) negative, she said.
Patients who developed JIA at a young age also were at increased risk, and the ocular complication typically occurred early in the course of disease.
Children with psoriatic arthritis also are at risk, but those with RF positive and systemic onset JIA are not.
“So we asked ourselves which at-risk patients would be eligible for anti-TNF-α treatment, and that would be those with oligoarticular disease; those with polyarticular, RF-negative disease; and those with psoriatic JIA,” she said.
A total of 434 patients fell into those groups; 45 of these had received anti-TNF-α treatment.
But once again Cox regression analysis found no difference in risk between those with and without anti-TNF-α treatment, she said.
“We concluded that anti-TNF-α therapy does not alter the risk for the development of new onset uveitis in children with JIA,” she said.
PTH Prevents First Fractures in Early Osteoporosis
SAN ANTONIO — Intact human recombinant parathyroid hormone prevented both recurrent and first fractures in a multinational, randomized, placebo-controlled study of postmenopausal women with osteoporosis, Mark P. Ettinger, M.D., said at the annual meeting of the American College of Rheumatology.
Previous studies have shown that the parathyroid hormone (PTH) analog teriperatide can prevent fractures in patients with advanced disease who already have had a fracture. The Treatment of Osteoporosis With PTH (TOP) study was the first to demonstrate the prevention of first fractures in patients with earlier disease, Dr. Ettinger said.
“This is extremely important, because the presence of any existing fracture greatly increases the risk of subsequent fractures,” he said in a late-breaking abstract session.
The TOP study included 2,532 women whose mean age was 64.4 years and whose mean spine, total hip, and femoral neck bone mineral density (BMD) T-scores were -3.0, -1.9, and -2.2, respectively.
The study population was very different from other osteoporosis treatment cohorts, in that the patients were younger, and only 19% already had fractures. In previous trials, fracture prevalence ranged from 37% to 100%, he said.
Patients were randomized to 100 mcg of subcutaneous PTH or placebo daily. All patients also took 700 mg calcium and 400 U vitamin D each day. A total of 1,737 patients completed the 18-month study.
At study completion, the vertebral fracture incidence was 3.3% in the placebo group and 1.1% in the PTH group, which represented a relative fracture risk reduction of 66%, said Dr. Ettinger, medical director emeritus of Radiant Research, Stuart, Fla.
In a per-protocol analysis, patients who had a fracture before entering the study had a 69% relative fracture risk reduction; those without a previous fracture had a risk reduction of 63%. At month 18 the mean spine, total hip, and femoral neck BMD had increased by 7.2%, 2.2%, and 2.5%, respectively, in the PTH group relative to the placebo group, he said.
About 9% of the PTH group withdrew because of headache, dizziness, nausea, or vomiting, or elevated serum or urine calcium levels. Overall, 16% of PTH patients and 12% of placebo patients withdrew during the course of the study. There were two deaths in the placebo group and one in the PTH group; this was judged to be unrelated to treatment.
“The results of the TOP study may change our treatment paradigm,” said Dr. Ettinger who disclosed that he received research grants and consulting fees from many pharmaceutical companies including NPS Pharmaceuticals, the Salt Lake City-based manufacturer of PTH.
SAN ANTONIO — Intact human recombinant parathyroid hormone prevented both recurrent and first fractures in a multinational, randomized, placebo-controlled study of postmenopausal women with osteoporosis, Mark P. Ettinger, M.D., said at the annual meeting of the American College of Rheumatology.
Previous studies have shown that the parathyroid hormone (PTH) analog teriperatide can prevent fractures in patients with advanced disease who already have had a fracture. The Treatment of Osteoporosis With PTH (TOP) study was the first to demonstrate the prevention of first fractures in patients with earlier disease, Dr. Ettinger said.
“This is extremely important, because the presence of any existing fracture greatly increases the risk of subsequent fractures,” he said in a late-breaking abstract session.
The TOP study included 2,532 women whose mean age was 64.4 years and whose mean spine, total hip, and femoral neck bone mineral density (BMD) T-scores were -3.0, -1.9, and -2.2, respectively.
The study population was very different from other osteoporosis treatment cohorts, in that the patients were younger, and only 19% already had fractures. In previous trials, fracture prevalence ranged from 37% to 100%, he said.
Patients were randomized to 100 mcg of subcutaneous PTH or placebo daily. All patients also took 700 mg calcium and 400 U vitamin D each day. A total of 1,737 patients completed the 18-month study.
At study completion, the vertebral fracture incidence was 3.3% in the placebo group and 1.1% in the PTH group, which represented a relative fracture risk reduction of 66%, said Dr. Ettinger, medical director emeritus of Radiant Research, Stuart, Fla.
In a per-protocol analysis, patients who had a fracture before entering the study had a 69% relative fracture risk reduction; those without a previous fracture had a risk reduction of 63%. At month 18 the mean spine, total hip, and femoral neck BMD had increased by 7.2%, 2.2%, and 2.5%, respectively, in the PTH group relative to the placebo group, he said.
About 9% of the PTH group withdrew because of headache, dizziness, nausea, or vomiting, or elevated serum or urine calcium levels. Overall, 16% of PTH patients and 12% of placebo patients withdrew during the course of the study. There were two deaths in the placebo group and one in the PTH group; this was judged to be unrelated to treatment.
“The results of the TOP study may change our treatment paradigm,” said Dr. Ettinger who disclosed that he received research grants and consulting fees from many pharmaceutical companies including NPS Pharmaceuticals, the Salt Lake City-based manufacturer of PTH.
SAN ANTONIO — Intact human recombinant parathyroid hormone prevented both recurrent and first fractures in a multinational, randomized, placebo-controlled study of postmenopausal women with osteoporosis, Mark P. Ettinger, M.D., said at the annual meeting of the American College of Rheumatology.
Previous studies have shown that the parathyroid hormone (PTH) analog teriperatide can prevent fractures in patients with advanced disease who already have had a fracture. The Treatment of Osteoporosis With PTH (TOP) study was the first to demonstrate the prevention of first fractures in patients with earlier disease, Dr. Ettinger said.
“This is extremely important, because the presence of any existing fracture greatly increases the risk of subsequent fractures,” he said in a late-breaking abstract session.
The TOP study included 2,532 women whose mean age was 64.4 years and whose mean spine, total hip, and femoral neck bone mineral density (BMD) T-scores were -3.0, -1.9, and -2.2, respectively.
The study population was very different from other osteoporosis treatment cohorts, in that the patients were younger, and only 19% already had fractures. In previous trials, fracture prevalence ranged from 37% to 100%, he said.
Patients were randomized to 100 mcg of subcutaneous PTH or placebo daily. All patients also took 700 mg calcium and 400 U vitamin D each day. A total of 1,737 patients completed the 18-month study.
At study completion, the vertebral fracture incidence was 3.3% in the placebo group and 1.1% in the PTH group, which represented a relative fracture risk reduction of 66%, said Dr. Ettinger, medical director emeritus of Radiant Research, Stuart, Fla.
In a per-protocol analysis, patients who had a fracture before entering the study had a 69% relative fracture risk reduction; those without a previous fracture had a risk reduction of 63%. At month 18 the mean spine, total hip, and femoral neck BMD had increased by 7.2%, 2.2%, and 2.5%, respectively, in the PTH group relative to the placebo group, he said.
About 9% of the PTH group withdrew because of headache, dizziness, nausea, or vomiting, or elevated serum or urine calcium levels. Overall, 16% of PTH patients and 12% of placebo patients withdrew during the course of the study. There were two deaths in the placebo group and one in the PTH group; this was judged to be unrelated to treatment.
“The results of the TOP study may change our treatment paradigm,” said Dr. Ettinger who disclosed that he received research grants and consulting fees from many pharmaceutical companies including NPS Pharmaceuticals, the Salt Lake City-based manufacturer of PTH.