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BARCELONA — Combining the anticlotting agent dipyridamole with low-dose prednisone led to a rapid decrease in rheumatoid arthritis disease activity, according to Dr. John R. Kirwan, speaking at the annual European Congress of Rheumatology.
The effects of glucocorticoids on inflammatory cells in rheumatoid arthritis (RA) include alterations in the expression of certain genes and intracellular metabolic pathways, said Dr. Kirwan, professor of rheumatic diseases at the Bristol Royal Infirmary (England).
“However, they do not affect all the genes involved in inflammation, they do not work completely, and they also upregulate some genes that cause side effects,” Dr. Kirwan explained in an interview.
This weak interaction becomes stronger in the presence of dipyridamole, amplifying the anti-inflammatory effects. Because the prednisone dose is low, fewer side effects would be expected, he said.
The double-blind study included 59 patients with Disease Activity Scores (DAS28) greater than 4.5 and C-reactive protein (CRP) levels of 2.2 mg/L or higher. Participants' mean age was 59 years, three-quarters were women, and almost all were white. Stable background methotrexate and nonsteroidal anti-inflammatory drugs were allowed, but no oral glucocorticoids were allowed for at least a month prior to enrollment.
Patients were randomized to receive the combination, known as CRx-102, or placebo for 6 weeks. The combination regimen is 2 mg prednisone with 200 mg dipyridamole at 8 a.m. and 1 mg prednisone plus 200 mg dipyridamole at 1 p.m. At day 42, 63% of patients receiving CRx-102 achieved an American College of Rheumatology (ACR) 20 response rate, as did 30% of patients receiving placebo. The difference was statistically significant.
Significant differences between the groups also were seen on DAS28, patient and physician global assessments, pain, and Health Assessment Questionnaire score, Dr. Kirwan wrote in a poster.
CRP levels fell significantly, decreasing by 50% by day seven. The most common adverse events, headache and gastrointestinal disturbances, were reported by 15% of patients receiving the active therapy.
“CRx-102 produced a clinically meaningful and rapid decrease in disease activity as assessed by DAS28, ACR 20, and CRP. These data suggest that this is a well-tolerated oral therapy that can be safely added to disease-modifying antirheumatic drugs in RA,” he concluded.
Dr. Kirwan was principal investigator on this study, which was sponsored by CombinatoRx Inc., Cambridge, Mass.
ELSEVIER GLOBAL MEDICAL NEWS
BARCELONA — Combining the anticlotting agent dipyridamole with low-dose prednisone led to a rapid decrease in rheumatoid arthritis disease activity, according to Dr. John R. Kirwan, speaking at the annual European Congress of Rheumatology.
The effects of glucocorticoids on inflammatory cells in rheumatoid arthritis (RA) include alterations in the expression of certain genes and intracellular metabolic pathways, said Dr. Kirwan, professor of rheumatic diseases at the Bristol Royal Infirmary (England).
“However, they do not affect all the genes involved in inflammation, they do not work completely, and they also upregulate some genes that cause side effects,” Dr. Kirwan explained in an interview.
This weak interaction becomes stronger in the presence of dipyridamole, amplifying the anti-inflammatory effects. Because the prednisone dose is low, fewer side effects would be expected, he said.
The double-blind study included 59 patients with Disease Activity Scores (DAS28) greater than 4.5 and C-reactive protein (CRP) levels of 2.2 mg/L or higher. Participants' mean age was 59 years, three-quarters were women, and almost all were white. Stable background methotrexate and nonsteroidal anti-inflammatory drugs were allowed, but no oral glucocorticoids were allowed for at least a month prior to enrollment.
Patients were randomized to receive the combination, known as CRx-102, or placebo for 6 weeks. The combination regimen is 2 mg prednisone with 200 mg dipyridamole at 8 a.m. and 1 mg prednisone plus 200 mg dipyridamole at 1 p.m. At day 42, 63% of patients receiving CRx-102 achieved an American College of Rheumatology (ACR) 20 response rate, as did 30% of patients receiving placebo. The difference was statistically significant.
Significant differences between the groups also were seen on DAS28, patient and physician global assessments, pain, and Health Assessment Questionnaire score, Dr. Kirwan wrote in a poster.
CRP levels fell significantly, decreasing by 50% by day seven. The most common adverse events, headache and gastrointestinal disturbances, were reported by 15% of patients receiving the active therapy.
“CRx-102 produced a clinically meaningful and rapid decrease in disease activity as assessed by DAS28, ACR 20, and CRP. These data suggest that this is a well-tolerated oral therapy that can be safely added to disease-modifying antirheumatic drugs in RA,” he concluded.
Dr. Kirwan was principal investigator on this study, which was sponsored by CombinatoRx Inc., Cambridge, Mass.
ELSEVIER GLOBAL MEDICAL NEWS
BARCELONA — Combining the anticlotting agent dipyridamole with low-dose prednisone led to a rapid decrease in rheumatoid arthritis disease activity, according to Dr. John R. Kirwan, speaking at the annual European Congress of Rheumatology.
The effects of glucocorticoids on inflammatory cells in rheumatoid arthritis (RA) include alterations in the expression of certain genes and intracellular metabolic pathways, said Dr. Kirwan, professor of rheumatic diseases at the Bristol Royal Infirmary (England).
“However, they do not affect all the genes involved in inflammation, they do not work completely, and they also upregulate some genes that cause side effects,” Dr. Kirwan explained in an interview.
This weak interaction becomes stronger in the presence of dipyridamole, amplifying the anti-inflammatory effects. Because the prednisone dose is low, fewer side effects would be expected, he said.
The double-blind study included 59 patients with Disease Activity Scores (DAS28) greater than 4.5 and C-reactive protein (CRP) levels of 2.2 mg/L or higher. Participants' mean age was 59 years, three-quarters were women, and almost all were white. Stable background methotrexate and nonsteroidal anti-inflammatory drugs were allowed, but no oral glucocorticoids were allowed for at least a month prior to enrollment.
Patients were randomized to receive the combination, known as CRx-102, or placebo for 6 weeks. The combination regimen is 2 mg prednisone with 200 mg dipyridamole at 8 a.m. and 1 mg prednisone plus 200 mg dipyridamole at 1 p.m. At day 42, 63% of patients receiving CRx-102 achieved an American College of Rheumatology (ACR) 20 response rate, as did 30% of patients receiving placebo. The difference was statistically significant.
Significant differences between the groups also were seen on DAS28, patient and physician global assessments, pain, and Health Assessment Questionnaire score, Dr. Kirwan wrote in a poster.
CRP levels fell significantly, decreasing by 50% by day seven. The most common adverse events, headache and gastrointestinal disturbances, were reported by 15% of patients receiving the active therapy.
“CRx-102 produced a clinically meaningful and rapid decrease in disease activity as assessed by DAS28, ACR 20, and CRP. These data suggest that this is a well-tolerated oral therapy that can be safely added to disease-modifying antirheumatic drugs in RA,” he concluded.
Dr. Kirwan was principal investigator on this study, which was sponsored by CombinatoRx Inc., Cambridge, Mass.
ELSEVIER GLOBAL MEDICAL NEWS