Rheumatoid Arthritis

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

LOS ANGELES — A review of data on 281 psoriasis patients found that those who began smoking after psoriasis onset developed psoriatic arthritis later than did nonsmokers or people who smoked before their psoriasis appeared.

Previous data suggest that psoriatic arthritis typically occurs approximately 10 years after the onset of psoriasis. In this study, the interval between diagnoses of psoriasis and psoriatic arthritis was 13 years in nonsmokers, 8 years in people who smoked before developing psoriasis, and 23 years in people who began smoking after their psoriasis diagnosis, Dr. Tina Rakkhit said.

That “dramatically longer time” to the development of joint disease in people who take up smoking after developing psoriasis “is consistent with the notion that the biology of psoriasis can be modulated by smoking activity,” she said at the annual meeting of the Society for Investigational Dermatology.

Of course, that doesn't mean that physicians should advocate smoking in patients with psoriasis.

The health hazards of smoking are well known. If the physiologic underpinnings of these findings can be elucidated, however, this may lead to preventive therapies for psoriatic arthritis without the toxicities of smoking, said Dr. Rakkhit, a dermatologic research fellow at the University of Utah, Salt Lake City.

“Our data support the concept that agents without such detrimental effects could be used to delay and possibly prevent the onset of this significant comorbid state,” Dr. Rakkhit and her associates concluded.

The data came from the 812-person Utah Psoriasis Initiative, a prospective, phenotypic database.

The study excluded patients who developed psoriatic arthritis before being diagnosed with psoriasis, which generally accounts for 15% of people with the joint disease.

Because the Utah Psoriasis Initiative does not collect data on measures of joint disease, the investigators could not tell whether the delayed psoriatic arthritis was less or more severe than earlier-appearing joint disease.

Compared with the general population of Utah, 13% of whom smoke, 36% of the study cohort smoked at the time of their psoriasis diagnosis. In the United States, 20% of the population smokes.

Psoriatic arthritis appeared in nonsmokers at an average age of 26 years and in smokers at age 29 in the current study. Patients were diagnosed with psoriatic arthritis at an average age of 36 if they never smoked and at age 42 if they ever smoked.

The findings add to the intriguing medical literature on the relationships between smoking and inflammatory diseases. Other studies suggest that heavier smokers develop rheumatoid arthritis later, Dr. Rakkhit noted. Crohn's disease appears earlier in smokers, and patients who undergo surgical correction for Crohn's disease are more likely to have recurrent disease. The opposite is seen with ulcerative colitis, which mainly is a disease of nonsmokers and former smokers. Among patients undergoing immunosuppressive therapies, a shorter duration is more likely to suffice in smokers than in nonsmokers.

LOS ANGELES — A review of data on 281 psoriasis patients found that those who began smoking after psoriasis onset developed psoriatic arthritis later than did nonsmokers or people who smoked before their psoriasis appeared.

Previous data suggest that psoriatic arthritis typically occurs approximately 10 years after the onset of psoriasis. In this study, the interval between diagnoses of psoriasis and psoriatic arthritis was 13 years in nonsmokers, 8 years in people who smoked before developing psoriasis, and 23 years in people who began smoking after their psoriasis diagnosis, Dr. Tina Rakkhit said.

That “dramatically longer time” to the development of joint disease in people who take up smoking after developing psoriasis “is consistent with the notion that the biology of psoriasis can be modulated by smoking activity,” she said at the annual meeting of the Society for Investigational Dermatology.

Of course, that doesn't mean that physicians should advocate smoking in patients with psoriasis.

The health hazards of smoking are well known. If the physiologic underpinnings of these findings can be elucidated, however, this may lead to preventive therapies for psoriatic arthritis without the toxicities of smoking, said Dr. Rakkhit, a dermatologic research fellow at the University of Utah, Salt Lake City.

“Our data support the concept that agents without such detrimental effects could be used to delay and possibly prevent the onset of this significant comorbid state,” Dr. Rakkhit and her associates concluded.

The data came from the 812-person Utah Psoriasis Initiative, a prospective, phenotypic database.

The study excluded patients who developed psoriatic arthritis before being diagnosed with psoriasis, which generally accounts for 15% of people with the joint disease.

Because the Utah Psoriasis Initiative does not collect data on measures of joint disease, the investigators could not tell whether the delayed psoriatic arthritis was less or more severe than earlier-appearing joint disease.

Compared with the general population of Utah, 13% of whom smoke, 36% of the study cohort smoked at the time of their psoriasis diagnosis. In the United States, 20% of the population smokes.

Psoriatic arthritis appeared in nonsmokers at an average age of 26 years and in smokers at age 29 in the current study. Patients were diagnosed with psoriatic arthritis at an average age of 36 if they never smoked and at age 42 if they ever smoked.

The findings add to the intriguing medical literature on the relationships between smoking and inflammatory diseases. Other studies suggest that heavier smokers develop rheumatoid arthritis later, Dr. Rakkhit noted. Crohn's disease appears earlier in smokers, and patients who undergo surgical correction for Crohn's disease are more likely to have recurrent disease. The opposite is seen with ulcerative colitis, which mainly is a disease of nonsmokers and former smokers. Among patients undergoing immunosuppressive therapies, a shorter duration is more likely to suffice in smokers than in nonsmokers.

LOS ANGELES — A review of data on 281 psoriasis patients found that those who began smoking after psoriasis onset developed psoriatic arthritis later than did nonsmokers or people who smoked before their psoriasis appeared.

Previous data suggest that psoriatic arthritis typically occurs approximately 10 years after the onset of psoriasis. In this study, the interval between diagnoses of psoriasis and psoriatic arthritis was 13 years in nonsmokers, 8 years in people who smoked before developing psoriasis, and 23 years in people who began smoking after their psoriasis diagnosis, Dr. Tina Rakkhit said.

That “dramatically longer time” to the development of joint disease in people who take up smoking after developing psoriasis “is consistent with the notion that the biology of psoriasis can be modulated by smoking activity,” she said at the annual meeting of the Society for Investigational Dermatology.

Of course, that doesn't mean that physicians should advocate smoking in patients with psoriasis.

The health hazards of smoking are well known. If the physiologic underpinnings of these findings can be elucidated, however, this may lead to preventive therapies for psoriatic arthritis without the toxicities of smoking, said Dr. Rakkhit, a dermatologic research fellow at the University of Utah, Salt Lake City.

“Our data support the concept that agents without such detrimental effects could be used to delay and possibly prevent the onset of this significant comorbid state,” Dr. Rakkhit and her associates concluded.

The data came from the 812-person Utah Psoriasis Initiative, a prospective, phenotypic database.

The study excluded patients who developed psoriatic arthritis before being diagnosed with psoriasis, which generally accounts for 15% of people with the joint disease.

Because the Utah Psoriasis Initiative does not collect data on measures of joint disease, the investigators could not tell whether the delayed psoriatic arthritis was less or more severe than earlier-appearing joint disease.

Compared with the general population of Utah, 13% of whom smoke, 36% of the study cohort smoked at the time of their psoriasis diagnosis. In the United States, 20% of the population smokes.

Psoriatic arthritis appeared in nonsmokers at an average age of 26 years and in smokers at age 29 in the current study. Patients were diagnosed with psoriatic arthritis at an average age of 36 if they never smoked and at age 42 if they ever smoked.

The findings add to the intriguing medical literature on the relationships between smoking and inflammatory diseases. Other studies suggest that heavier smokers develop rheumatoid arthritis later, Dr. Rakkhit noted. Crohn's disease appears earlier in smokers, and patients who undergo surgical correction for Crohn's disease are more likely to have recurrent disease. The opposite is seen with ulcerative colitis, which mainly is a disease of nonsmokers and former smokers. Among patients undergoing immunosuppressive therapies, a shorter duration is more likely to suffice in smokers than in nonsmokers.

BARCELONA — Patients with rheumatoid arthritis who are undergoing repeat courses of treatment with rituximab should begin re-treatment promptly once symptoms begin to recur, Dr. Philip J. Mease said at the annual European Congress of Rheumatology.

This conclusion emerged from analysis of the open-label extension phase of the Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis (REFLEX) trial, a double-blind, placebo-controlled multicenter study in which 298 patient initially received the active drug treatment.

All patients had failed at least one tumor necrosis factor blocker prior to beginning treatment with the B-cell-depleting agent. Those randomized to active treatment received two doses of rituximab, 1,000 mg, 2 weeks apart, plus stable doses of methotrexate.

Patients who achieved a 20% or greater improvement in swollen and tender joint counts during the 24-week blinded phase of the study were eligible to enter the open-label phase; 168 did so and had adequate follow-up for analysis 24 weeks after the second course of rituximab.

The four components of the 28-joint disease activity score (DAS28)—swollen joint count, tender joint count, erythrocyte sedimentation rate, and patient's global assessment—were assessed before each course of rituximab treatment, and every 4–8 weeks thereafter.

Mean DAS28 was 6.89 before the first course of rituximab and 6.12 before the second course, Dr. Mease wrote in a poster. The second course was administered at a median time of 43 weeks after the first course.

A generalized linear mixed model fit to all visits after the second course was used to evaluate the effects of various variables on DAS28, including pretrial patient and disease characteristics, DAS28 and Health Assessment Questionnaire at various times, and peripheral CD19+ B cell count before courses.

According to the model, DAS28 after the second course of treatment was independently increased by three factors: DAS28 before the second course, DAS28 at trial week 20, and Health Assessment Questionnaire at week 16.

Every 1 point that DAS28 was allowed to worsen before the second course of rituximab resulted in a 0.32-point higher DAS28 after the second course, according to Dr. Mease, who is a rheumatologist in Seattle.

Equally significant in the model but with the opposite effect on DAS28 was the peripheral CD19+ B-cell count before the second course: A count of at least 80 u 103/mL before the second course resulted in a 0.47-point lower DAS28 after the second course.

“The take-home message from this analysis is that in order to achieve the best DAS with a repeat course of rituximab, the preferable time for re-treatment is when the patient is starting to have resurgent symptoms,” Dr. Mease commented in an interview.

“On average, patient response lasts 6 months and at that point clinicians should start monitoring more diligently, looking for signs of disease activity. If the patient waits until 8 months for re-treatment, the resulting DAS won't be as good,” Dr. Mease added.

REFLEX was supported by Genentech, Biogen, and Roche. Dr. Mease has previously disclosed receiving consulting fees from Genentech and Biogen.

Symptom resurgence usually occurs about 6 months after ending the first course. DR. MEASE

BARCELONA — Patients with rheumatoid arthritis who are undergoing repeat courses of treatment with rituximab should begin re-treatment promptly once symptoms begin to recur, Dr. Philip J. Mease said at the annual European Congress of Rheumatology.

This conclusion emerged from analysis of the open-label extension phase of the Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis (REFLEX) trial, a double-blind, placebo-controlled multicenter study in which 298 patient initially received the active drug treatment.

All patients had failed at least one tumor necrosis factor blocker prior to beginning treatment with the B-cell-depleting agent. Those randomized to active treatment received two doses of rituximab, 1,000 mg, 2 weeks apart, plus stable doses of methotrexate.

Patients who achieved a 20% or greater improvement in swollen and tender joint counts during the 24-week blinded phase of the study were eligible to enter the open-label phase; 168 did so and had adequate follow-up for analysis 24 weeks after the second course of rituximab.

The four components of the 28-joint disease activity score (DAS28)—swollen joint count, tender joint count, erythrocyte sedimentation rate, and patient's global assessment—were assessed before each course of rituximab treatment, and every 4–8 weeks thereafter.

Mean DAS28 was 6.89 before the first course of rituximab and 6.12 before the second course, Dr. Mease wrote in a poster. The second course was administered at a median time of 43 weeks after the first course.

A generalized linear mixed model fit to all visits after the second course was used to evaluate the effects of various variables on DAS28, including pretrial patient and disease characteristics, DAS28 and Health Assessment Questionnaire at various times, and peripheral CD19+ B cell count before courses.

According to the model, DAS28 after the second course of treatment was independently increased by three factors: DAS28 before the second course, DAS28 at trial week 20, and Health Assessment Questionnaire at week 16.

Every 1 point that DAS28 was allowed to worsen before the second course of rituximab resulted in a 0.32-point higher DAS28 after the second course, according to Dr. Mease, who is a rheumatologist in Seattle.

Equally significant in the model but with the opposite effect on DAS28 was the peripheral CD19+ B-cell count before the second course: A count of at least 80 u 103/mL before the second course resulted in a 0.47-point lower DAS28 after the second course.

“The take-home message from this analysis is that in order to achieve the best DAS with a repeat course of rituximab, the preferable time for re-treatment is when the patient is starting to have resurgent symptoms,” Dr. Mease commented in an interview.

“On average, patient response lasts 6 months and at that point clinicians should start monitoring more diligently, looking for signs of disease activity. If the patient waits until 8 months for re-treatment, the resulting DAS won't be as good,” Dr. Mease added.

REFLEX was supported by Genentech, Biogen, and Roche. Dr. Mease has previously disclosed receiving consulting fees from Genentech and Biogen.

Symptom resurgence usually occurs about 6 months after ending the first course. DR. MEASE

BARCELONA — Patients with rheumatoid arthritis who are undergoing repeat courses of treatment with rituximab should begin re-treatment promptly once symptoms begin to recur, Dr. Philip J. Mease said at the annual European Congress of Rheumatology.

This conclusion emerged from analysis of the open-label extension phase of the Randomized Evaluation of Long-Term Efficacy of Rituximab in Rheumatoid Arthritis (REFLEX) trial, a double-blind, placebo-controlled multicenter study in which 298 patient initially received the active drug treatment.

All patients had failed at least one tumor necrosis factor blocker prior to beginning treatment with the B-cell-depleting agent. Those randomized to active treatment received two doses of rituximab, 1,000 mg, 2 weeks apart, plus stable doses of methotrexate.

Patients who achieved a 20% or greater improvement in swollen and tender joint counts during the 24-week blinded phase of the study were eligible to enter the open-label phase; 168 did so and had adequate follow-up for analysis 24 weeks after the second course of rituximab.

The four components of the 28-joint disease activity score (DAS28)—swollen joint count, tender joint count, erythrocyte sedimentation rate, and patient's global assessment—were assessed before each course of rituximab treatment, and every 4–8 weeks thereafter.

Mean DAS28 was 6.89 before the first course of rituximab and 6.12 before the second course, Dr. Mease wrote in a poster. The second course was administered at a median time of 43 weeks after the first course.

A generalized linear mixed model fit to all visits after the second course was used to evaluate the effects of various variables on DAS28, including pretrial patient and disease characteristics, DAS28 and Health Assessment Questionnaire at various times, and peripheral CD19+ B cell count before courses.

According to the model, DAS28 after the second course of treatment was independently increased by three factors: DAS28 before the second course, DAS28 at trial week 20, and Health Assessment Questionnaire at week 16.

Every 1 point that DAS28 was allowed to worsen before the second course of rituximab resulted in a 0.32-point higher DAS28 after the second course, according to Dr. Mease, who is a rheumatologist in Seattle.

Equally significant in the model but with the opposite effect on DAS28 was the peripheral CD19+ B-cell count before the second course: A count of at least 80 u 103/mL before the second course resulted in a 0.47-point lower DAS28 after the second course.

“The take-home message from this analysis is that in order to achieve the best DAS with a repeat course of rituximab, the preferable time for re-treatment is when the patient is starting to have resurgent symptoms,” Dr. Mease commented in an interview.

“On average, patient response lasts 6 months and at that point clinicians should start monitoring more diligently, looking for signs of disease activity. If the patient waits until 8 months for re-treatment, the resulting DAS won't be as good,” Dr. Mease added.

REFLEX was supported by Genentech, Biogen, and Roche. Dr. Mease has previously disclosed receiving consulting fees from Genentech and Biogen.

Symptom resurgence usually occurs about 6 months after ending the first course. DR. MEASE

Magnetic resonance imaging detects inflammation in the sacroiliac joints in affected patients early in the course of ankylosing spondylitis when no chronic changes are detectable on radiograph, said Prof. Jürgen Braun, medical director of Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Herne (Germany).

The spinal stiffness and loss of spinal mobility that are often the presenting symptoms of ankylosing spondylitis result from spinal inflammation and/or structural damage that is in turn triggered primarily by osteoproliferation rather than osteodestruction. Inflammation is assumed to trigger new bone formation. However, no close correlation between inflammation and osteoproliferation has been found so far.

Sacroiliitis is a hallmark of the disease, especially in early stages. However, radiographs of the sacroiliac joints can appear normal in the early phase of the disease, meaning that structural changes might not be apparent for several years. The inability of radiographs to detect chronic changes can lead to diagnostic delay in ankylosing spondylitis. MRI has proved to be useful in the detection of axial inflammation in very early stages of the disease, commented Dr. Braun.

Used with an imaging technique called short tau inversion recovery (STIR) that does not require contrast agents, MRI also can identify sacroiliitis and spondylitis in patients with other spondyloarthritides including the undifferentiated form that progresses into ankylosing spondylitis in more than 50% of the cases. In one study, MRI of sacroiliac joints was able to predict the development of structural radiographic changes in these joints with a positive predictive value of 60%, 3 years before the changes occurred (J. Rheumatol. 1999;26:1953–8).

While the use of MRI to detect chronic changes continues to be under investigation, radiographs offer a more sensitive way to detect existing structural changes. “Therefore, a radiograph of the sacroiliac joints is always needed, especially at early disease stages,” he said, noting that 20%–30% of patients will already have developed structural changes within the first 2 years of inflammatory back pain.

MRI also appears to be useful for the detection of enthesitis and synovitis, not only in the axial skeleton but also in the peripheral joints and entheses.

Several medications have been available for the treatment of ankylosing spondylitis, with varying degrees of efficacy. But the introduction of the tumor necrosis factor (TNF) blockers has been a substantial development for patients with the disease. Earlier diagnosis could translate into earlier use of these effective medications and preservation of joint architecture.

Three agents are currently approved for ankylosing spondylitis: the monoclonal chimeric antibody infliximab (Remicade), the fully humanized monoclonal adalimumab (Humira), and the recombinant human soluble TNF-α receptor fusion protein etanercept (Enbrel).

MRI may have a role in assessing response to therapy. “Clinical disease activity and spinal inflammation as detected by MRI are substantially reduced by TNF blockers, as shown after short-term and long-term anti-TNF therapy,” said Dr. Braun. On the basis of two recent studies it appears unlikely that the treatment with TNF blockers is able to completely halt radiographic progression. However, recent long-term data on anti-TNF-α therapy in ankylosing spondylitis suggested that function and mobility of the patients who were consistently treated over 5 years is preserved in an improved state, compared with baseline.

Inflammatory lesions of the sacroiliac joint are seen with STIR technique MRI.

Inflammatory lesions can also be seen in the spine using STIR technique MRI. Photos courtesy Dr. Xenofon Baraliakos

Magnetic resonance imaging detects inflammation in the sacroiliac joints in affected patients early in the course of ankylosing spondylitis when no chronic changes are detectable on radiograph, said Prof. Jürgen Braun, medical director of Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Herne (Germany).

The spinal stiffness and loss of spinal mobility that are often the presenting symptoms of ankylosing spondylitis result from spinal inflammation and/or structural damage that is in turn triggered primarily by osteoproliferation rather than osteodestruction. Inflammation is assumed to trigger new bone formation. However, no close correlation between inflammation and osteoproliferation has been found so far.

Sacroiliitis is a hallmark of the disease, especially in early stages. However, radiographs of the sacroiliac joints can appear normal in the early phase of the disease, meaning that structural changes might not be apparent for several years. The inability of radiographs to detect chronic changes can lead to diagnostic delay in ankylosing spondylitis. MRI has proved to be useful in the detection of axial inflammation in very early stages of the disease, commented Dr. Braun.

Used with an imaging technique called short tau inversion recovery (STIR) that does not require contrast agents, MRI also can identify sacroiliitis and spondylitis in patients with other spondyloarthritides including the undifferentiated form that progresses into ankylosing spondylitis in more than 50% of the cases. In one study, MRI of sacroiliac joints was able to predict the development of structural radiographic changes in these joints with a positive predictive value of 60%, 3 years before the changes occurred (J. Rheumatol. 1999;26:1953–8).

While the use of MRI to detect chronic changes continues to be under investigation, radiographs offer a more sensitive way to detect existing structural changes. “Therefore, a radiograph of the sacroiliac joints is always needed, especially at early disease stages,” he said, noting that 20%–30% of patients will already have developed structural changes within the first 2 years of inflammatory back pain.

MRI also appears to be useful for the detection of enthesitis and synovitis, not only in the axial skeleton but also in the peripheral joints and entheses.

Several medications have been available for the treatment of ankylosing spondylitis, with varying degrees of efficacy. But the introduction of the tumor necrosis factor (TNF) blockers has been a substantial development for patients with the disease. Earlier diagnosis could translate into earlier use of these effective medications and preservation of joint architecture.

Three agents are currently approved for ankylosing spondylitis: the monoclonal chimeric antibody infliximab (Remicade), the fully humanized monoclonal adalimumab (Humira), and the recombinant human soluble TNF-α receptor fusion protein etanercept (Enbrel).

MRI may have a role in assessing response to therapy. “Clinical disease activity and spinal inflammation as detected by MRI are substantially reduced by TNF blockers, as shown after short-term and long-term anti-TNF therapy,” said Dr. Braun. On the basis of two recent studies it appears unlikely that the treatment with TNF blockers is able to completely halt radiographic progression. However, recent long-term data on anti-TNF-α therapy in ankylosing spondylitis suggested that function and mobility of the patients who were consistently treated over 5 years is preserved in an improved state, compared with baseline.

Inflammatory lesions of the sacroiliac joint are seen with STIR technique MRI.

Inflammatory lesions can also be seen in the spine using STIR technique MRI. Photos courtesy Dr. Xenofon Baraliakos

Magnetic resonance imaging detects inflammation in the sacroiliac joints in affected patients early in the course of ankylosing spondylitis when no chronic changes are detectable on radiograph, said Prof. Jürgen Braun, medical director of Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Herne (Germany).

The spinal stiffness and loss of spinal mobility that are often the presenting symptoms of ankylosing spondylitis result from spinal inflammation and/or structural damage that is in turn triggered primarily by osteoproliferation rather than osteodestruction. Inflammation is assumed to trigger new bone formation. However, no close correlation between inflammation and osteoproliferation has been found so far.

Sacroiliitis is a hallmark of the disease, especially in early stages. However, radiographs of the sacroiliac joints can appear normal in the early phase of the disease, meaning that structural changes might not be apparent for several years. The inability of radiographs to detect chronic changes can lead to diagnostic delay in ankylosing spondylitis. MRI has proved to be useful in the detection of axial inflammation in very early stages of the disease, commented Dr. Braun.

Used with an imaging technique called short tau inversion recovery (STIR) that does not require contrast agents, MRI also can identify sacroiliitis and spondylitis in patients with other spondyloarthritides including the undifferentiated form that progresses into ankylosing spondylitis in more than 50% of the cases. In one study, MRI of sacroiliac joints was able to predict the development of structural radiographic changes in these joints with a positive predictive value of 60%, 3 years before the changes occurred (J. Rheumatol. 1999;26:1953–8).

While the use of MRI to detect chronic changes continues to be under investigation, radiographs offer a more sensitive way to detect existing structural changes. “Therefore, a radiograph of the sacroiliac joints is always needed, especially at early disease stages,” he said, noting that 20%–30% of patients will already have developed structural changes within the first 2 years of inflammatory back pain.

MRI also appears to be useful for the detection of enthesitis and synovitis, not only in the axial skeleton but also in the peripheral joints and entheses.

Several medications have been available for the treatment of ankylosing spondylitis, with varying degrees of efficacy. But the introduction of the tumor necrosis factor (TNF) blockers has been a substantial development for patients with the disease. Earlier diagnosis could translate into earlier use of these effective medications and preservation of joint architecture.

Three agents are currently approved for ankylosing spondylitis: the monoclonal chimeric antibody infliximab (Remicade), the fully humanized monoclonal adalimumab (Humira), and the recombinant human soluble TNF-α receptor fusion protein etanercept (Enbrel).

MRI may have a role in assessing response to therapy. “Clinical disease activity and spinal inflammation as detected by MRI are substantially reduced by TNF blockers, as shown after short-term and long-term anti-TNF therapy,” said Dr. Braun. On the basis of two recent studies it appears unlikely that the treatment with TNF blockers is able to completely halt radiographic progression. However, recent long-term data on anti-TNF-α therapy in ankylosing spondylitis suggested that function and mobility of the patients who were consistently treated over 5 years is preserved in an improved state, compared with baseline.

Inflammatory lesions of the sacroiliac joint are seen with STIR technique MRI.

Inflammatory lesions can also be seen in the spine using STIR technique MRI. Photos courtesy Dr. Xenofon Baraliakos

BIRMINGHAM, ENGLAND — Nearly half of all patients who initially failed therapy with anti-tumor necrosis factor-α agents benefited following a switch to a second or third drug in the class, according to a study presented at the annual meeting of the British Society for Rheumatology.

Dr. Jemma Pringle and associates studied 153 rheumatology patients who had a mean disease duration of 12 years upon entrance to a registry between 2001 and 2006. The patients' median initial disease activity score (DAS) was 7.55.

A cohort of 53 patients stopped their initial anti-TNF-α agent. Of these, 23 stopped due to an adverse event and 30 from loss of efficacy. Of the 33 who received a second anti-TNF-α agent, 22 responded and have remained on the drug for a median of 19 months at the time of her presentation, Dr. Pringle said.

The other 11 stopped anti-TNF-α therapy because of side effects and/or a lack of efficacy. Patients experienced a mean decrease in DAS of 32% from baseline to 4.15 after they undertook treatment with an alternative anti-TNF-α agent.

Of the seven participants who eventually switched to a third drug, four responded and continued to take the drug for a median of 6 months. There was a 44% mean decrease in baseline DAS among these patients.

“Nearly half of these are presently continuing their second or third agent with a clinically significant response,” said Dr. Pringle, a rheumatologist at Gartnavel General Hospital, Glasgow, Scotland.

Up to 40% of patients do not respond to their initial anti-TNF-α drug, commented Dr. Pringle.

However, because each of the different anti-TNF-α agents have different properties, Dr. Pringle advised sticking with the class before considering other therapies, despite the fact that switching patients to a second anti-TNF-α agent is not as cost effective (since second response rates are lower), as one meeting attendee pointed out.

BIRMINGHAM, ENGLAND — Nearly half of all patients who initially failed therapy with anti-tumor necrosis factor-α agents benefited following a switch to a second or third drug in the class, according to a study presented at the annual meeting of the British Society for Rheumatology.

Dr. Jemma Pringle and associates studied 153 rheumatology patients who had a mean disease duration of 12 years upon entrance to a registry between 2001 and 2006. The patients' median initial disease activity score (DAS) was 7.55.

A cohort of 53 patients stopped their initial anti-TNF-α agent. Of these, 23 stopped due to an adverse event and 30 from loss of efficacy. Of the 33 who received a second anti-TNF-α agent, 22 responded and have remained on the drug for a median of 19 months at the time of her presentation, Dr. Pringle said.

The other 11 stopped anti-TNF-α therapy because of side effects and/or a lack of efficacy. Patients experienced a mean decrease in DAS of 32% from baseline to 4.15 after they undertook treatment with an alternative anti-TNF-α agent.

Of the seven participants who eventually switched to a third drug, four responded and continued to take the drug for a median of 6 months. There was a 44% mean decrease in baseline DAS among these patients.

“Nearly half of these are presently continuing their second or third agent with a clinically significant response,” said Dr. Pringle, a rheumatologist at Gartnavel General Hospital, Glasgow, Scotland.

Up to 40% of patients do not respond to their initial anti-TNF-α drug, commented Dr. Pringle.

However, because each of the different anti-TNF-α agents have different properties, Dr. Pringle advised sticking with the class before considering other therapies, despite the fact that switching patients to a second anti-TNF-α agent is not as cost effective (since second response rates are lower), as one meeting attendee pointed out.

BIRMINGHAM, ENGLAND — Nearly half of all patients who initially failed therapy with anti-tumor necrosis factor-α agents benefited following a switch to a second or third drug in the class, according to a study presented at the annual meeting of the British Society for Rheumatology.

Dr. Jemma Pringle and associates studied 153 rheumatology patients who had a mean disease duration of 12 years upon entrance to a registry between 2001 and 2006. The patients' median initial disease activity score (DAS) was 7.55.

A cohort of 53 patients stopped their initial anti-TNF-α agent. Of these, 23 stopped due to an adverse event and 30 from loss of efficacy. Of the 33 who received a second anti-TNF-α agent, 22 responded and have remained on the drug for a median of 19 months at the time of her presentation, Dr. Pringle said.

The other 11 stopped anti-TNF-α therapy because of side effects and/or a lack of efficacy. Patients experienced a mean decrease in DAS of 32% from baseline to 4.15 after they undertook treatment with an alternative anti-TNF-α agent.

Of the seven participants who eventually switched to a third drug, four responded and continued to take the drug for a median of 6 months. There was a 44% mean decrease in baseline DAS among these patients.

“Nearly half of these are presently continuing their second or third agent with a clinically significant response,” said Dr. Pringle, a rheumatologist at Gartnavel General Hospital, Glasgow, Scotland.

Up to 40% of patients do not respond to their initial anti-TNF-α drug, commented Dr. Pringle.

However, because each of the different anti-TNF-α agents have different properties, Dr. Pringle advised sticking with the class before considering other therapies, despite the fact that switching patients to a second anti-TNF-α agent is not as cost effective (since second response rates are lower), as one meeting attendee pointed out.

BALTIMORE — A new understanding of the “anemia of inflammation” may help point the way to new treatments in the future, but in the meantime it illustrates why iron supplementation does not raise hemoglobin levels in patients with rheumatoid arthritis and other inflammatory diseases, Dr. Joan Bathon said at a conference on rheumatic diseases sponsored by the Johns Hopkins University.

Formerly known as “anemia of chronic diseases” because it is commonly seen in inflammatory diseases such as rheumatoid arthritis (RA) as well as in chronic infections and some cancers, the condition is now known by the term “anemia of inflammation,” which better reflects its etiology. It is not the result of bleeding, hemolysis, nutritional deficit (vitamin B₁₂, folate, iron), or a marrow disorder, said Dr. Bathon, professor of medicine at Johns Hopkins, Baltimore.

Lacking an understanding of the underlying etiology, health care providers will often give these patients iron supplementation. However, “we know that iron treatment does not really alleviate this anemia,” she said.

Anemia is extremely common among RA patients. In a study comparing 2,120 consecutive RA patients (contributing 26,221 hemoglobin determinations) with 3,843 patients who had noninflammatory rheumatic disorders (7,251 hemoglobin determinations) seen between 1974 and 2004 in a clinical practice setting, the prevalence of chronic anemia was 35.3% when a hemoglobin cutoff of less than 12 g/dL was used.

Hemoglobin levels were consistently lower among the RA patients than among those with noninflammatory conditions, by a mean of 0.8 g/dL.

Those data, reported at the 2005 American College of Rheumatology meeting by Dr. Frederick Wolfe of the National Data Bank for Rheumatic Diseases, Wichita, Kan., suggest that “more than one-third of patients with RA are anemic, if you use a broad definition,” according to Dr. Bathon.

That study also found that among the RA patients, lower hemoglobin was associated with high disease activity; C-reactive protein levels were strongly predictive of anemia; and quality of life was reduced by 5.5% among the patients with anemia after adjustment for age and gender.

In general, patients with anemia of inflammation have decreased total circulating iron levels and binding capacity, yet their total body iron (ferritin) stores are increased.

At the same time, erythropoietin production is blunted, as is the response to endogenous erythropoietin. Red blood cell survival is modestly decreased. “Exogenous iron and/or exogenous erythropoietin do not fully resolve the anemia,” she said.

Although iron is essential for oxygen transport and other vital functions, it also generates free radicals that can lead to oxidative damage, manifesting in conditions such as atherosclerosis, diabetes, or cancer.

But humans can't eliminate excess iron. Therefore, uptake from the gastrointestinal tract is tightly regulated and efficiently recycled. “No matter how much you give orally, there's only a limited amount the body can pick up,” Dr. Bathon explained.

Recently, a small peptide hormone called hepcidin was identified as the principal regulator of systemic iron homeostasis. Synthesized in the liver, hepcidin inhibits the intestinal absorption of iron and suppresses release of iron from macrophage and hepatocyte stores.

Measurement of hepcidin levels is now being investigated as a possible diagnostic tool for various iron disorders. In one study, a novel urine hepcidin assay using mass spectrometry was able to discriminate among patients with secondary iron overload, iron-deficient anemia, and hereditary hemochromatosis (Blood 2005;106:3268–70).

Hepcidin production would be expected to be increased in RA patients, but that hasn't been studied, Dr. Bathon said.

Other data suggest that interleukin-6—but not interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α)—promotes anemia of inflammation by synthesizing hepcidin (J. Clin. Invest. 2004;113:1271–6), and some investigators have suggested that an antibody directed against IL-6 might therefore offer potential treatment for inflammation-induced anemia (Ann. Rheum. Dis. 2000;59 [Suppl. 1]:i21–7).

But, even though TNF-α and IL-1 don't induce hepcidin in some models, it's not clear whether the process is entirely mediated by IL-6.

In fact, treatment of RA patients with TNF-α blockers often does improve their anemia. It's not yet clear which treatment would be a better method—inhibition of IL-6 or TNF—for resolving anemia inflammation, Dr. Bathon said.

The role of erythropoietin for treating anemia of inflammation is also currently unclear. Although the response to exogenous erythropoietin tends to be blunted in RA patients in proportion to the severity of their inflammation, data from a few small studies do suggest that the treatment may nonetheless be beneficial by lessening their anemia.

One such study, involving 17 patients who received a total 32 weeks of treatment, showed an overall excellent hematologic response without toxicity but with no meaningful change in rheumatologic clinical status (Am. J. Med. 1990;89:161–8).

More recently, 30 patients with RA and anemia were treated with 150 IU/kg recombinant human erythropoietin twice weekly for 12 weeks, along with 200 mg of intravenous iron sucrose per week in the 23 patients who developed functional iron deficiency.

Average hemoglobin increased from 10.7 to 13.2 g/dL after a mean treatment period of 8 weeks. With recombinant human erythrpoietin treatment, patients also experienced increased muscle strength, decreased fatigue, fewer swollen or tender joints, and other improvements in disease activity variables (J. Rheumatol. 2001;28:2430–6).

But, Dr. Bathon said in an interview with RHEUMATOLOGY NEWS, erythropoietin “hasn't been studied enough to provide guidelines for its use, except perhaps prior to surgery where a lot of bleeding is anticipated.”

Moreover, “it's kind of fallen by the wayside,” in large part because “treatment of RA largely resolves the anemia.”

Indeed, it may simply be that addressing the cause of the underlying inflammation—in RA, infections, or other chronic conditions—will correct its accompanying anemia as well.

BALTIMORE — A new understanding of the “anemia of inflammation” may help point the way to new treatments in the future, but in the meantime it illustrates why iron supplementation does not raise hemoglobin levels in patients with rheumatoid arthritis and other inflammatory diseases, Dr. Joan Bathon said at a conference on rheumatic diseases sponsored by the Johns Hopkins University.

Formerly known as “anemia of chronic diseases” because it is commonly seen in inflammatory diseases such as rheumatoid arthritis (RA) as well as in chronic infections and some cancers, the condition is now known by the term “anemia of inflammation,” which better reflects its etiology. It is not the result of bleeding, hemolysis, nutritional deficit (vitamin B₁₂, folate, iron), or a marrow disorder, said Dr. Bathon, professor of medicine at Johns Hopkins, Baltimore.

Lacking an understanding of the underlying etiology, health care providers will often give these patients iron supplementation. However, “we know that iron treatment does not really alleviate this anemia,” she said.

Anemia is extremely common among RA patients. In a study comparing 2,120 consecutive RA patients (contributing 26,221 hemoglobin determinations) with 3,843 patients who had noninflammatory rheumatic disorders (7,251 hemoglobin determinations) seen between 1974 and 2004 in a clinical practice setting, the prevalence of chronic anemia was 35.3% when a hemoglobin cutoff of less than 12 g/dL was used.

Hemoglobin levels were consistently lower among the RA patients than among those with noninflammatory conditions, by a mean of 0.8 g/dL.

Those data, reported at the 2005 American College of Rheumatology meeting by Dr. Frederick Wolfe of the National Data Bank for Rheumatic Diseases, Wichita, Kan., suggest that “more than one-third of patients with RA are anemic, if you use a broad definition,” according to Dr. Bathon.

That study also found that among the RA patients, lower hemoglobin was associated with high disease activity; C-reactive protein levels were strongly predictive of anemia; and quality of life was reduced by 5.5% among the patients with anemia after adjustment for age and gender.

In general, patients with anemia of inflammation have decreased total circulating iron levels and binding capacity, yet their total body iron (ferritin) stores are increased.

At the same time, erythropoietin production is blunted, as is the response to endogenous erythropoietin. Red blood cell survival is modestly decreased. “Exogenous iron and/or exogenous erythropoietin do not fully resolve the anemia,” she said.

Although iron is essential for oxygen transport and other vital functions, it also generates free radicals that can lead to oxidative damage, manifesting in conditions such as atherosclerosis, diabetes, or cancer.

But humans can't eliminate excess iron. Therefore, uptake from the gastrointestinal tract is tightly regulated and efficiently recycled. “No matter how much you give orally, there's only a limited amount the body can pick up,” Dr. Bathon explained.

Recently, a small peptide hormone called hepcidin was identified as the principal regulator of systemic iron homeostasis. Synthesized in the liver, hepcidin inhibits the intestinal absorption of iron and suppresses release of iron from macrophage and hepatocyte stores.

Measurement of hepcidin levels is now being investigated as a possible diagnostic tool for various iron disorders. In one study, a novel urine hepcidin assay using mass spectrometry was able to discriminate among patients with secondary iron overload, iron-deficient anemia, and hereditary hemochromatosis (Blood 2005;106:3268–70).

Hepcidin production would be expected to be increased in RA patients, but that hasn't been studied, Dr. Bathon said.

Other data suggest that interleukin-6—but not interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α)—promotes anemia of inflammation by synthesizing hepcidin (J. Clin. Invest. 2004;113:1271–6), and some investigators have suggested that an antibody directed against IL-6 might therefore offer potential treatment for inflammation-induced anemia (Ann. Rheum. Dis. 2000;59 [Suppl. 1]:i21–7).

But, even though TNF-α and IL-1 don't induce hepcidin in some models, it's not clear whether the process is entirely mediated by IL-6.

In fact, treatment of RA patients with TNF-α blockers often does improve their anemia. It's not yet clear which treatment would be a better method—inhibition of IL-6 or TNF—for resolving anemia inflammation, Dr. Bathon said.

The role of erythropoietin for treating anemia of inflammation is also currently unclear. Although the response to exogenous erythropoietin tends to be blunted in RA patients in proportion to the severity of their inflammation, data from a few small studies do suggest that the treatment may nonetheless be beneficial by lessening their anemia.

One such study, involving 17 patients who received a total 32 weeks of treatment, showed an overall excellent hematologic response without toxicity but with no meaningful change in rheumatologic clinical status (Am. J. Med. 1990;89:161–8).

More recently, 30 patients with RA and anemia were treated with 150 IU/kg recombinant human erythropoietin twice weekly for 12 weeks, along with 200 mg of intravenous iron sucrose per week in the 23 patients who developed functional iron deficiency.

Average hemoglobin increased from 10.7 to 13.2 g/dL after a mean treatment period of 8 weeks. With recombinant human erythrpoietin treatment, patients also experienced increased muscle strength, decreased fatigue, fewer swollen or tender joints, and other improvements in disease activity variables (J. Rheumatol. 2001;28:2430–6).

But, Dr. Bathon said in an interview with RHEUMATOLOGY NEWS, erythropoietin “hasn't been studied enough to provide guidelines for its use, except perhaps prior to surgery where a lot of bleeding is anticipated.”

Moreover, “it's kind of fallen by the wayside,” in large part because “treatment of RA largely resolves the anemia.”

Indeed, it may simply be that addressing the cause of the underlying inflammation—in RA, infections, or other chronic conditions—will correct its accompanying anemia as well.

BALTIMORE — A new understanding of the “anemia of inflammation” may help point the way to new treatments in the future, but in the meantime it illustrates why iron supplementation does not raise hemoglobin levels in patients with rheumatoid arthritis and other inflammatory diseases, Dr. Joan Bathon said at a conference on rheumatic diseases sponsored by the Johns Hopkins University.

Formerly known as “anemia of chronic diseases” because it is commonly seen in inflammatory diseases such as rheumatoid arthritis (RA) as well as in chronic infections and some cancers, the condition is now known by the term “anemia of inflammation,” which better reflects its etiology. It is not the result of bleeding, hemolysis, nutritional deficit (vitamin B₁₂, folate, iron), or a marrow disorder, said Dr. Bathon, professor of medicine at Johns Hopkins, Baltimore.

Lacking an understanding of the underlying etiology, health care providers will often give these patients iron supplementation. However, “we know that iron treatment does not really alleviate this anemia,” she said.

Anemia is extremely common among RA patients. In a study comparing 2,120 consecutive RA patients (contributing 26,221 hemoglobin determinations) with 3,843 patients who had noninflammatory rheumatic disorders (7,251 hemoglobin determinations) seen between 1974 and 2004 in a clinical practice setting, the prevalence of chronic anemia was 35.3% when a hemoglobin cutoff of less than 12 g/dL was used.

Hemoglobin levels were consistently lower among the RA patients than among those with noninflammatory conditions, by a mean of 0.8 g/dL.

Those data, reported at the 2005 American College of Rheumatology meeting by Dr. Frederick Wolfe of the National Data Bank for Rheumatic Diseases, Wichita, Kan., suggest that “more than one-third of patients with RA are anemic, if you use a broad definition,” according to Dr. Bathon.

That study also found that among the RA patients, lower hemoglobin was associated with high disease activity; C-reactive protein levels were strongly predictive of anemia; and quality of life was reduced by 5.5% among the patients with anemia after adjustment for age and gender.

In general, patients with anemia of inflammation have decreased total circulating iron levels and binding capacity, yet their total body iron (ferritin) stores are increased.

At the same time, erythropoietin production is blunted, as is the response to endogenous erythropoietin. Red blood cell survival is modestly decreased. “Exogenous iron and/or exogenous erythropoietin do not fully resolve the anemia,” she said.

Although iron is essential for oxygen transport and other vital functions, it also generates free radicals that can lead to oxidative damage, manifesting in conditions such as atherosclerosis, diabetes, or cancer.

But humans can't eliminate excess iron. Therefore, uptake from the gastrointestinal tract is tightly regulated and efficiently recycled. “No matter how much you give orally, there's only a limited amount the body can pick up,” Dr. Bathon explained.

Recently, a small peptide hormone called hepcidin was identified as the principal regulator of systemic iron homeostasis. Synthesized in the liver, hepcidin inhibits the intestinal absorption of iron and suppresses release of iron from macrophage and hepatocyte stores.

Measurement of hepcidin levels is now being investigated as a possible diagnostic tool for various iron disorders. In one study, a novel urine hepcidin assay using mass spectrometry was able to discriminate among patients with secondary iron overload, iron-deficient anemia, and hereditary hemochromatosis (Blood 2005;106:3268–70).

Hepcidin production would be expected to be increased in RA patients, but that hasn't been studied, Dr. Bathon said.

Other data suggest that interleukin-6—but not interleukin-1 (IL-1) or tumor necrosis factor-α (TNF-α)—promotes anemia of inflammation by synthesizing hepcidin (J. Clin. Invest. 2004;113:1271–6), and some investigators have suggested that an antibody directed against IL-6 might therefore offer potential treatment for inflammation-induced anemia (Ann. Rheum. Dis. 2000;59 [Suppl. 1]:i21–7).

But, even though TNF-α and IL-1 don't induce hepcidin in some models, it's not clear whether the process is entirely mediated by IL-6.

In fact, treatment of RA patients with TNF-α blockers often does improve their anemia. It's not yet clear which treatment would be a better method—inhibition of IL-6 or TNF—for resolving anemia inflammation, Dr. Bathon said.

The role of erythropoietin for treating anemia of inflammation is also currently unclear. Although the response to exogenous erythropoietin tends to be blunted in RA patients in proportion to the severity of their inflammation, data from a few small studies do suggest that the treatment may nonetheless be beneficial by lessening their anemia.

One such study, involving 17 patients who received a total 32 weeks of treatment, showed an overall excellent hematologic response without toxicity but with no meaningful change in rheumatologic clinical status (Am. J. Med. 1990;89:161–8).

More recently, 30 patients with RA and anemia were treated with 150 IU/kg recombinant human erythropoietin twice weekly for 12 weeks, along with 200 mg of intravenous iron sucrose per week in the 23 patients who developed functional iron deficiency.

Average hemoglobin increased from 10.7 to 13.2 g/dL after a mean treatment period of 8 weeks. With recombinant human erythrpoietin treatment, patients also experienced increased muscle strength, decreased fatigue, fewer swollen or tender joints, and other improvements in disease activity variables (J. Rheumatol. 2001;28:2430–6).

But, Dr. Bathon said in an interview with RHEUMATOLOGY NEWS, erythropoietin “hasn't been studied enough to provide guidelines for its use, except perhaps prior to surgery where a lot of bleeding is anticipated.”

Moreover, “it's kind of fallen by the wayside,” in large part because “treatment of RA largely resolves the anemia.”

Indeed, it may simply be that addressing the cause of the underlying inflammation—in RA, infections, or other chronic conditions—will correct its accompanying anemia as well.

Smoking appears to contribute to the development of knee cartilage loss and defects in individuals with a family history of knee osteoarthritis (OA), according to the results reported by Dr. Changhai Ding and associates of the University of Tasmania in Australia.

In this study the knee cartilage of 345 relatively young individuals (the average age was 45 years) were measured at baseline and again 2.3 years later, and their risk factors were assessed.

Of the 162 persons with at least one parent with severe primary knee OA, 40 current smokers had greater loss in medial and lateral tibial cartilage volumes (beta = −2.20% and −1.45%. respectively) than did 47 former smokers and 75 never-smokers, after adjusting for confounding factors in a logistic regression analysis. Pack-years of smoking were also significantly associated with changes in cartilage volume (Arthritis Rheum. 2007;56:1521–8).

Dr. Ding and associates did not find a similar relationship between smoking status and knee OA measures in 163 individuals with no family history of knee OA.

The only factor significantly associated with smoking status in control individuals was change in lateral tibiofemoral cartilage volume.

“This provides evidence for a gene-environment interaction in the etiology of knee OA,” the investigators wrote.

Among those with a family history of knee OA, being a current smoker increased the risk of developing medial tibiofemoral cartilage defects by nearly fivefold during the study period. Similarly, a positive family history increased the risk of lateral tibiofemoral cartilage defects threefold.

The risk increases among heavy smokers (at least 20 pack-years) versus never-smokers were 10-fold and 13-fold, respectively.

The interaction among smoking status, family history of knee OA, and cartilage effects remained significant in regards to change in medial tibial cartilage volume and increases in cartilage defects, both medial and lateral, even after adjusting for potentially confounding factors.

In the overall group, the prevalence of knee pain was higher among current smokers (41%) than it was among former smokers or never-smokers (33%), regardless of family history.

There was no overall association between smoking status and baseline tibial cartilage volume or prevalent tibiofemoral cartilage defects.

Smoking appears to contribute to the development of knee cartilage loss and defects in individuals with a family history of knee osteoarthritis (OA), according to the results reported by Dr. Changhai Ding and associates of the University of Tasmania in Australia.

In this study the knee cartilage of 345 relatively young individuals (the average age was 45 years) were measured at baseline and again 2.3 years later, and their risk factors were assessed.

Of the 162 persons with at least one parent with severe primary knee OA, 40 current smokers had greater loss in medial and lateral tibial cartilage volumes (beta = −2.20% and −1.45%. respectively) than did 47 former smokers and 75 never-smokers, after adjusting for confounding factors in a logistic regression analysis. Pack-years of smoking were also significantly associated with changes in cartilage volume (Arthritis Rheum. 2007;56:1521–8).

Dr. Ding and associates did not find a similar relationship between smoking status and knee OA measures in 163 individuals with no family history of knee OA.

The only factor significantly associated with smoking status in control individuals was change in lateral tibiofemoral cartilage volume.

“This provides evidence for a gene-environment interaction in the etiology of knee OA,” the investigators wrote.

Among those with a family history of knee OA, being a current smoker increased the risk of developing medial tibiofemoral cartilage defects by nearly fivefold during the study period. Similarly, a positive family history increased the risk of lateral tibiofemoral cartilage defects threefold.

The risk increases among heavy smokers (at least 20 pack-years) versus never-smokers were 10-fold and 13-fold, respectively.

The interaction among smoking status, family history of knee OA, and cartilage effects remained significant in regards to change in medial tibial cartilage volume and increases in cartilage defects, both medial and lateral, even after adjusting for potentially confounding factors.

In the overall group, the prevalence of knee pain was higher among current smokers (41%) than it was among former smokers or never-smokers (33%), regardless of family history.

There was no overall association between smoking status and baseline tibial cartilage volume or prevalent tibiofemoral cartilage defects.

Smoking appears to contribute to the development of knee cartilage loss and defects in individuals with a family history of knee osteoarthritis (OA), according to the results reported by Dr. Changhai Ding and associates of the University of Tasmania in Australia.

In this study the knee cartilage of 345 relatively young individuals (the average age was 45 years) were measured at baseline and again 2.3 years later, and their risk factors were assessed.

Of the 162 persons with at least one parent with severe primary knee OA, 40 current smokers had greater loss in medial and lateral tibial cartilage volumes (beta = −2.20% and −1.45%. respectively) than did 47 former smokers and 75 never-smokers, after adjusting for confounding factors in a logistic regression analysis. Pack-years of smoking were also significantly associated with changes in cartilage volume (Arthritis Rheum. 2007;56:1521–8).

Dr. Ding and associates did not find a similar relationship between smoking status and knee OA measures in 163 individuals with no family history of knee OA.

The only factor significantly associated with smoking status in control individuals was change in lateral tibiofemoral cartilage volume.

“This provides evidence for a gene-environment interaction in the etiology of knee OA,” the investigators wrote.

Among those with a family history of knee OA, being a current smoker increased the risk of developing medial tibiofemoral cartilage defects by nearly fivefold during the study period. Similarly, a positive family history increased the risk of lateral tibiofemoral cartilage defects threefold.

The risk increases among heavy smokers (at least 20 pack-years) versus never-smokers were 10-fold and 13-fold, respectively.

The interaction among smoking status, family history of knee OA, and cartilage effects remained significant in regards to change in medial tibial cartilage volume and increases in cartilage defects, both medial and lateral, even after adjusting for potentially confounding factors.

In the overall group, the prevalence of knee pain was higher among current smokers (41%) than it was among former smokers or never-smokers (33%), regardless of family history.

There was no overall association between smoking status and baseline tibial cartilage volume or prevalent tibiofemoral cartilage defects.

A new technique for delivering an old nonsteroidal anti-inflammatory drug is just as effective as oral celecoxib for relieving the pain of knee osteoarthritis, German researchers report.

The NSAID ketoprofen, approved in both the United States and Europe, when combined in a gel that is capable of penetrating the skin directly to arthritic joints, was significantly better than placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. Moreover, it did so without entering the systemic circulation, said Dr. Matthias Rother, head of research and development of IDEA AG, Munich, Germany, and colleagues.

The toxicities of systemic NSAID treatment are well known, and the newer COX-2 inhibitors are associated with elevated cardiovascular risks. Hence, the need for safer therapies, the investigators wrote.

The new technology, called Transfersome, is a special gel made up of nanoparticles too large to be absorbed into the microcirculatory barrier of the skin, Dr. Rother said in a telephone interview.

Numerous gel and cream NSAID preparations are available in Europe. All work by diffusion, with the drugs absorbed systemically when they are applied to the skin. But when an NSAID, in this case ketoprofen, is mixed with the nanoparticle gel, it is able to penetrate into deep muscle and joints and be released. The mixture of ketoprofen and Transfersomes is called IDEA-033, Dr. Rother said.

“Transfersomes are ultradeformable carriers loaded with an active substance and applied epicutaneously in an aqueous suspension. Once they are on the skin, the water in the suspension begins to evaporate, and this draws the carriers containing ketoprofen through the skin barrier to the specific target areas,” he explained.

To compare this form of ketoprofen delivery with celecoxib and placebo in the relief of knee OA, the investigators randomized patients for at least 6 months to either 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (138 patients), 100 mg oral celecoxib plus placebo gel (132 patients), or both placebo formulations (127 patients) twice a day for 6 weeks.

Efficacy was assessed by measuring the changes in the Western Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis pain subscale, physical function subscale, and patient global assessment (PGA) of response from baseline to the end of the study, in the index knee.

Overall, the mean WOMAC pain subscale scores were reduced by 18.2 in patients who received IDEA-033, by 20.3 in patients who received celecoxib, and by 9.9 in those patients who received placebo.

The mean physical function subscale score was reduced by 14.6 in patients who received IDEA-033, 16.6 in those receiving celecoxib, and 10.2 in the placebo group.

The mean PGA of response scores were 1.8 in the IDEA-033 group, 1.7 in the celecoxib group, and 1.3 in the placebo group.

The differences in change between IDEA-033 and placebo were statistically significant for pain subscale (P = .0041) and PGA of response (P = .0015).

Gastrointestinal adverse events with IDEA-033 were similar to placebo, the investigators wrote. No GI bleeding occurred. The rate of nonserious GI adverse events for IDEA-033, at 9.4%, was similar to placebo and numerically lower than for celecoxib (13.6%).

One patient treated with celecoxib had a myocardial infarction, one patient treated with placebo had angina, and no serious cardiovascular events occurred in patients treated with IDEA-033.

The IDEA-033 patients had more erythema and more skin irritations than the group receiving placebo gel, the investigators added (ARD Online First, published online by the British Medical Journal on March 15, 2007, as 10.1136/ard.2006.065128).

Systemic exposure in the IDEA-033 group was between 1% and 5%, compared with that of celecoxib, Dr. Rother said.

A new technique for delivering an old nonsteroidal anti-inflammatory drug is just as effective as oral celecoxib for relieving the pain of knee osteoarthritis, German researchers report.

The NSAID ketoprofen, approved in both the United States and Europe, when combined in a gel that is capable of penetrating the skin directly to arthritic joints, was significantly better than placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. Moreover, it did so without entering the systemic circulation, said Dr. Matthias Rother, head of research and development of IDEA AG, Munich, Germany, and colleagues.

The toxicities of systemic NSAID treatment are well known, and the newer COX-2 inhibitors are associated with elevated cardiovascular risks. Hence, the need for safer therapies, the investigators wrote.

The new technology, called Transfersome, is a special gel made up of nanoparticles too large to be absorbed into the microcirculatory barrier of the skin, Dr. Rother said in a telephone interview.

Numerous gel and cream NSAID preparations are available in Europe. All work by diffusion, with the drugs absorbed systemically when they are applied to the skin. But when an NSAID, in this case ketoprofen, is mixed with the nanoparticle gel, it is able to penetrate into deep muscle and joints and be released. The mixture of ketoprofen and Transfersomes is called IDEA-033, Dr. Rother said.

“Transfersomes are ultradeformable carriers loaded with an active substance and applied epicutaneously in an aqueous suspension. Once they are on the skin, the water in the suspension begins to evaporate, and this draws the carriers containing ketoprofen through the skin barrier to the specific target areas,” he explained.

To compare this form of ketoprofen delivery with celecoxib and placebo in the relief of knee OA, the investigators randomized patients for at least 6 months to either 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (138 patients), 100 mg oral celecoxib plus placebo gel (132 patients), or both placebo formulations (127 patients) twice a day for 6 weeks.

Efficacy was assessed by measuring the changes in the Western Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis pain subscale, physical function subscale, and patient global assessment (PGA) of response from baseline to the end of the study, in the index knee.

Overall, the mean WOMAC pain subscale scores were reduced by 18.2 in patients who received IDEA-033, by 20.3 in patients who received celecoxib, and by 9.9 in those patients who received placebo.

The mean physical function subscale score was reduced by 14.6 in patients who received IDEA-033, 16.6 in those receiving celecoxib, and 10.2 in the placebo group.

The mean PGA of response scores were 1.8 in the IDEA-033 group, 1.7 in the celecoxib group, and 1.3 in the placebo group.

The differences in change between IDEA-033 and placebo were statistically significant for pain subscale (P = .0041) and PGA of response (P = .0015).

Gastrointestinal adverse events with IDEA-033 were similar to placebo, the investigators wrote. No GI bleeding occurred. The rate of nonserious GI adverse events for IDEA-033, at 9.4%, was similar to placebo and numerically lower than for celecoxib (13.6%).

One patient treated with celecoxib had a myocardial infarction, one patient treated with placebo had angina, and no serious cardiovascular events occurred in patients treated with IDEA-033.

The IDEA-033 patients had more erythema and more skin irritations than the group receiving placebo gel, the investigators added (ARD Online First, published online by the British Medical Journal on March 15, 2007, as 10.1136/ard.2006.065128).

Systemic exposure in the IDEA-033 group was between 1% and 5%, compared with that of celecoxib, Dr. Rother said.

A new technique for delivering an old nonsteroidal anti-inflammatory drug is just as effective as oral celecoxib for relieving the pain of knee osteoarthritis, German researchers report.

The NSAID ketoprofen, approved in both the United States and Europe, when combined in a gel that is capable of penetrating the skin directly to arthritic joints, was significantly better than placebo and comparable with celecoxib in relieving pain associated with an acute flare of knee osteoarthritis. Moreover, it did so without entering the systemic circulation, said Dr. Matthias Rother, head of research and development of IDEA AG, Munich, Germany, and colleagues.

The toxicities of systemic NSAID treatment are well known, and the newer COX-2 inhibitors are associated with elevated cardiovascular risks. Hence, the need for safer therapies, the investigators wrote.

The new technology, called Transfersome, is a special gel made up of nanoparticles too large to be absorbed into the microcirculatory barrier of the skin, Dr. Rother said in a telephone interview.

Numerous gel and cream NSAID preparations are available in Europe. All work by diffusion, with the drugs absorbed systemically when they are applied to the skin. But when an NSAID, in this case ketoprofen, is mixed with the nanoparticle gel, it is able to penetrate into deep muscle and joints and be released. The mixture of ketoprofen and Transfersomes is called IDEA-033, Dr. Rother said.

“Transfersomes are ultradeformable carriers loaded with an active substance and applied epicutaneously in an aqueous suspension. Once they are on the skin, the water in the suspension begins to evaporate, and this draws the carriers containing ketoprofen through the skin barrier to the specific target areas,” he explained.

To compare this form of ketoprofen delivery with celecoxib and placebo in the relief of knee OA, the investigators randomized patients for at least 6 months to either 110 mg epicutaneous ketoprofen in 4.8 g Transfersome plus oral placebo (138 patients), 100 mg oral celecoxib plus placebo gel (132 patients), or both placebo formulations (127 patients) twice a day for 6 weeks.

Efficacy was assessed by measuring the changes in the Western Ontario and McMaster Universities (WOMAC) Index of Osteoarthritis pain subscale, physical function subscale, and patient global assessment (PGA) of response from baseline to the end of the study, in the index knee.

Overall, the mean WOMAC pain subscale scores were reduced by 18.2 in patients who received IDEA-033, by 20.3 in patients who received celecoxib, and by 9.9 in those patients who received placebo.

The mean physical function subscale score was reduced by 14.6 in patients who received IDEA-033, 16.6 in those receiving celecoxib, and 10.2 in the placebo group.

The mean PGA of response scores were 1.8 in the IDEA-033 group, 1.7 in the celecoxib group, and 1.3 in the placebo group.

The differences in change between IDEA-033 and placebo were statistically significant for pain subscale (P = .0041) and PGA of response (P = .0015).

Gastrointestinal adverse events with IDEA-033 were similar to placebo, the investigators wrote. No GI bleeding occurred. The rate of nonserious GI adverse events for IDEA-033, at 9.4%, was similar to placebo and numerically lower than for celecoxib (13.6%).

One patient treated with celecoxib had a myocardial infarction, one patient treated with placebo had angina, and no serious cardiovascular events occurred in patients treated with IDEA-033.

The IDEA-033 patients had more erythema and more skin irritations than the group receiving placebo gel, the investigators added (ARD Online First, published online by the British Medical Journal on March 15, 2007, as 10.1136/ard.2006.065128).

Systemic exposure in the IDEA-033 group was between 1% and 5%, compared with that of celecoxib, Dr. Rother said.

The placebo effect appears to account for most of the improvements associated with acupuncture for osteoarthritis of the knee, according to an analysis of nine trials.

But Eric Manheimer of the Center for Integrative Medicine at University of Maryland, Baltimore, and his associates also appeared to identify at least a small biologic effect of the procedure, since patients who received genuine acupuncture in sham-controlled trials experienced some short-term improvements in both pain and function.

Still, Mr. Manheimer, field administrator in the complementary medicine program concluded, “It is too soon to recommend acupuncture as a routine part of care for patients with osteoarthritis.”

The analysis included 11 randomized controlled trials conducted from 1999 to 2003 and comprised more than 1,000 patients with knee osteoarthritis. Four studies compared acupuncture with wait list. The other seven studies included a sham treatment. Nine of the 11 studies included enough outcomes data to be included in the pooled analysis (Ann. Intern. Med. 2007;146:868–77).

Acupuncture, as compared with the sham control, provided some improvements in pain and function, both in the short term and at 6 months, but these were deemed clinically irrelevant.

Compared with wait-listed patients, those who received acupuncture reported clinically relevant improvements in pain and function, which were sustained at 6 months.

The sham-controlled trials all used different sham procedures, including a combination of penetrating and nonpenetrating needles; needles inserted away from acupuncture points; and patch electrodes delivering current.

This made it difficult to decipher the treatment response, since it was impossible to tell how many patients receiving the various sham treatments truly believed they could be getting real acupuncture. Additionally, two sham protocols involving the use of penetrating needles placed away from acupuncture points were judged possibly to have exerted some biologically active effect.

The observation of any improvement, however clinically irrelevant, suggested that acupuncture might be a biologically active procedure, according to the authors. They cautioned, however, that the placebo response probably plays a large role. “The fact that both the acupuncture and sham groups reported greater improvements than [did] those of the usual care control groups suggests that acupuncture may elicit a greater placebo effect … than usual care therapies.”

The study may have been limited by the possibility that wait-listed patients were given inaccurate assessments of their actual response to care.

“Patient expectations that acupuncture will work may also affect those on a waiting list. By having to wait for a treatment that they believe is effective, patients waiting for acupuncture may have been disappointed by the delay, which may influence their ratings of subjective outcomes while waiting.”

Several large controlled trials are still ongoing, and at least one additional trial has been completed but remains unpublished. The results of these studies may further elucidate what role, if any, acupuncture may have in the treatment of knee osteoarthritis, the researchers noted.

In Western medicine, it is believed that the needles stimulate endorphins. ©MarkThomas/Science Photo Library

The placebo effect appears to account for most of the improvements associated with acupuncture for osteoarthritis of the knee, according to an analysis of nine trials.

But Eric Manheimer of the Center for Integrative Medicine at University of Maryland, Baltimore, and his associates also appeared to identify at least a small biologic effect of the procedure, since patients who received genuine acupuncture in sham-controlled trials experienced some short-term improvements in both pain and function.

Still, Mr. Manheimer, field administrator in the complementary medicine program concluded, “It is too soon to recommend acupuncture as a routine part of care for patients with osteoarthritis.”

The analysis included 11 randomized controlled trials conducted from 1999 to 2003 and comprised more than 1,000 patients with knee osteoarthritis. Four studies compared acupuncture with wait list. The other seven studies included a sham treatment. Nine of the 11 studies included enough outcomes data to be included in the pooled analysis (Ann. Intern. Med. 2007;146:868–77).

Acupuncture, as compared with the sham control, provided some improvements in pain and function, both in the short term and at 6 months, but these were deemed clinically irrelevant.

Compared with wait-listed patients, those who received acupuncture reported clinically relevant improvements in pain and function, which were sustained at 6 months.

The sham-controlled trials all used different sham procedures, including a combination of penetrating and nonpenetrating needles; needles inserted away from acupuncture points; and patch electrodes delivering current.

This made it difficult to decipher the treatment response, since it was impossible to tell how many patients receiving the various sham treatments truly believed they could be getting real acupuncture. Additionally, two sham protocols involving the use of penetrating needles placed away from acupuncture points were judged possibly to have exerted some biologically active effect.

The observation of any improvement, however clinically irrelevant, suggested that acupuncture might be a biologically active procedure, according to the authors. They cautioned, however, that the placebo response probably plays a large role. “The fact that both the acupuncture and sham groups reported greater improvements than [did] those of the usual care control groups suggests that acupuncture may elicit a greater placebo effect … than usual care therapies.”

The study may have been limited by the possibility that wait-listed patients were given inaccurate assessments of their actual response to care.

“Patient expectations that acupuncture will work may also affect those on a waiting list. By having to wait for a treatment that they believe is effective, patients waiting for acupuncture may have been disappointed by the delay, which may influence their ratings of subjective outcomes while waiting.”

Several large controlled trials are still ongoing, and at least one additional trial has been completed but remains unpublished. The results of these studies may further elucidate what role, if any, acupuncture may have in the treatment of knee osteoarthritis, the researchers noted.

In Western medicine, it is believed that the needles stimulate endorphins. ©MarkThomas/Science Photo Library

The placebo effect appears to account for most of the improvements associated with acupuncture for osteoarthritis of the knee, according to an analysis of nine trials.

But Eric Manheimer of the Center for Integrative Medicine at University of Maryland, Baltimore, and his associates also appeared to identify at least a small biologic effect of the procedure, since patients who received genuine acupuncture in sham-controlled trials experienced some short-term improvements in both pain and function.

Still, Mr. Manheimer, field administrator in the complementary medicine program concluded, “It is too soon to recommend acupuncture as a routine part of care for patients with osteoarthritis.”

The analysis included 11 randomized controlled trials conducted from 1999 to 2003 and comprised more than 1,000 patients with knee osteoarthritis. Four studies compared acupuncture with wait list. The other seven studies included a sham treatment. Nine of the 11 studies included enough outcomes data to be included in the pooled analysis (Ann. Intern. Med. 2007;146:868–77).

Acupuncture, as compared with the sham control, provided some improvements in pain and function, both in the short term and at 6 months, but these were deemed clinically irrelevant.

Compared with wait-listed patients, those who received acupuncture reported clinically relevant improvements in pain and function, which were sustained at 6 months.

The sham-controlled trials all used different sham procedures, including a combination of penetrating and nonpenetrating needles; needles inserted away from acupuncture points; and patch electrodes delivering current.

This made it difficult to decipher the treatment response, since it was impossible to tell how many patients receiving the various sham treatments truly believed they could be getting real acupuncture. Additionally, two sham protocols involving the use of penetrating needles placed away from acupuncture points were judged possibly to have exerted some biologically active effect.

The observation of any improvement, however clinically irrelevant, suggested that acupuncture might be a biologically active procedure, according to the authors. They cautioned, however, that the placebo response probably plays a large role. “The fact that both the acupuncture and sham groups reported greater improvements than [did] those of the usual care control groups suggests that acupuncture may elicit a greater placebo effect … than usual care therapies.”

The study may have been limited by the possibility that wait-listed patients were given inaccurate assessments of their actual response to care.

“Patient expectations that acupuncture will work may also affect those on a waiting list. By having to wait for a treatment that they believe is effective, patients waiting for acupuncture may have been disappointed by the delay, which may influence their ratings of subjective outcomes while waiting.”

Several large controlled trials are still ongoing, and at least one additional trial has been completed but remains unpublished. The results of these studies may further elucidate what role, if any, acupuncture may have in the treatment of knee osteoarthritis, the researchers noted.

In Western medicine, it is believed that the needles stimulate endorphins. ©MarkThomas/Science Photo Library

BIRMINGHAM, ENGLAND — Adding adalimumab therapy to existing treatment of patients with rheumatoid arthritis might be a worthwhile step to drive some patients into remission, according to a large study presented at the annual meeting of the British Society for Rheumatology.

More than one-third of 6,610 long-term rheumatoid arthritis patients achieved remission at any point in the Research in Active Rheumatoid Arthritis (ReAct) study. Remission was achieved despite an average of three prior disease-modifying antirheumatic drugs and an average disease activity score (DAS) of 6.0 at baseline.

In contrast to a clinical trial that might exclude heavily pretreated patients or those with more severe disease, this open-label, multinational study was designed “to mimic day-to-day practices as best we could,” Dr. Paul Wordsworth said.

Participants received 40 mg adalimumab (Humira, Abbott) subcutaneously every other week for 12 weeks added to existing therapy with standard disease-modifying antirheumatic drugs, glucocorticoids and/or nonsteroidal anti-inflammatory drugs.

Patients could opt to continue the adjunctive therapy beyond 12 weeks. The mean duration of adalimumab treatment was 7 months. The mean age of participants was 54 years.

Overall, 81% of the participants in the study were female.

A subset of 1,251 patients continued adalimumab up to 52 weeks. At 1 year, 13% of patients were in remission for at least 6 months, defined as achievement of American College of Rheumatology 70% improvement criteria (ACR70).

The addition of adalimumab to standard therapy led to clinical remission defined as a DAS28 below 2.6 in 38% of all patients at any time during the study.

Remission was sustained at least 6 weeks by 21% of patients. A total of 20% achieved a DAS28 below 2.6 at week 12 and 25% at last observation, said Dr. Wordsworth, professor of clinical rheumatology, Nuffield Orthopaedic Centre, Oxford, England.

Researchers also assessed patients according to the simplified disease activity index (3.3 or less was considered remission), the clinical disease activity index, and the tender and swollen joint count.

Although it is difficult to conclude from this study if duration of therapy should go beyond 12 weeks, the percentage of patients who experienced clinical remission increased beyond this time point irrespective of the assessment method, Dr. Wordsworth said.

“There was a significant proportion of patients who had remission or significant improvement after 3 months,” he added.

Dr. Wordsworth disclosed that he is a consultant for Abbott, which makes adalimumab.

BIRMINGHAM, ENGLAND — Adding adalimumab therapy to existing treatment of patients with rheumatoid arthritis might be a worthwhile step to drive some patients into remission, according to a large study presented at the annual meeting of the British Society for Rheumatology.

More than one-third of 6,610 long-term rheumatoid arthritis patients achieved remission at any point in the Research in Active Rheumatoid Arthritis (ReAct) study. Remission was achieved despite an average of three prior disease-modifying antirheumatic drugs and an average disease activity score (DAS) of 6.0 at baseline.

In contrast to a clinical trial that might exclude heavily pretreated patients or those with more severe disease, this open-label, multinational study was designed “to mimic day-to-day practices as best we could,” Dr. Paul Wordsworth said.

Participants received 40 mg adalimumab (Humira, Abbott) subcutaneously every other week for 12 weeks added to existing therapy with standard disease-modifying antirheumatic drugs, glucocorticoids and/or nonsteroidal anti-inflammatory drugs.

Patients could opt to continue the adjunctive therapy beyond 12 weeks. The mean duration of adalimumab treatment was 7 months. The mean age of participants was 54 years.

Overall, 81% of the participants in the study were female.

A subset of 1,251 patients continued adalimumab up to 52 weeks. At 1 year, 13% of patients were in remission for at least 6 months, defined as achievement of American College of Rheumatology 70% improvement criteria (ACR70).

The addition of adalimumab to standard therapy led to clinical remission defined as a DAS28 below 2.6 in 38% of all patients at any time during the study.

Remission was sustained at least 6 weeks by 21% of patients. A total of 20% achieved a DAS28 below 2.6 at week 12 and 25% at last observation, said Dr. Wordsworth, professor of clinical rheumatology, Nuffield Orthopaedic Centre, Oxford, England.

Researchers also assessed patients according to the simplified disease activity index (3.3 or less was considered remission), the clinical disease activity index, and the tender and swollen joint count.

Although it is difficult to conclude from this study if duration of therapy should go beyond 12 weeks, the percentage of patients who experienced clinical remission increased beyond this time point irrespective of the assessment method, Dr. Wordsworth said.

“There was a significant proportion of patients who had remission or significant improvement after 3 months,” he added.

Dr. Wordsworth disclosed that he is a consultant for Abbott, which makes adalimumab.

BIRMINGHAM, ENGLAND — Adding adalimumab therapy to existing treatment of patients with rheumatoid arthritis might be a worthwhile step to drive some patients into remission, according to a large study presented at the annual meeting of the British Society for Rheumatology.

More than one-third of 6,610 long-term rheumatoid arthritis patients achieved remission at any point in the Research in Active Rheumatoid Arthritis (ReAct) study. Remission was achieved despite an average of three prior disease-modifying antirheumatic drugs and an average disease activity score (DAS) of 6.0 at baseline.

In contrast to a clinical trial that might exclude heavily pretreated patients or those with more severe disease, this open-label, multinational study was designed “to mimic day-to-day practices as best we could,” Dr. Paul Wordsworth said.

Participants received 40 mg adalimumab (Humira, Abbott) subcutaneously every other week for 12 weeks added to existing therapy with standard disease-modifying antirheumatic drugs, glucocorticoids and/or nonsteroidal anti-inflammatory drugs.

Patients could opt to continue the adjunctive therapy beyond 12 weeks. The mean duration of adalimumab treatment was 7 months. The mean age of participants was 54 years.

Overall, 81% of the participants in the study were female.

A subset of 1,251 patients continued adalimumab up to 52 weeks. At 1 year, 13% of patients were in remission for at least 6 months, defined as achievement of American College of Rheumatology 70% improvement criteria (ACR70).

The addition of adalimumab to standard therapy led to clinical remission defined as a DAS28 below 2.6 in 38% of all patients at any time during the study.

Remission was sustained at least 6 weeks by 21% of patients. A total of 20% achieved a DAS28 below 2.6 at week 12 and 25% at last observation, said Dr. Wordsworth, professor of clinical rheumatology, Nuffield Orthopaedic Centre, Oxford, England.

Researchers also assessed patients according to the simplified disease activity index (3.3 or less was considered remission), the clinical disease activity index, and the tender and swollen joint count.

Although it is difficult to conclude from this study if duration of therapy should go beyond 12 weeks, the percentage of patients who experienced clinical remission increased beyond this time point irrespective of the assessment method, Dr. Wordsworth said.

“There was a significant proportion of patients who had remission or significant improvement after 3 months,” he added.

Dr. Wordsworth disclosed that he is a consultant for Abbott, which makes adalimumab.