Rheumatoid Arthritis

The risk for a postsurgical gout flare is greatest in patients with high presurgical serum urate levels, patients who've had cancer surgery, and in those who did not receive presurgical colchicine, according to a study.

Dr. Eun Bong Lee of the Seoul (South Korea) National University and colleagues looked at 67 patients who had a postsurgical gout attack and 67 who did not. All had prior histories of gout (Ann. Rheum. Dis. 2007 Nov. 12 [Epub doi:10.1136/ard.2007.078683]).

In an interview, Dr. Lee said “the postsurgical gout attack develops within 14 days after the surgery,” although the mean in this study was 4 days.

Lower extremity joints were affected in 65 of the 67 patients (97%) with a postsurgical gout flare. The most common site was the first metatarsophalangeal (MTP) joint (42 patients, or 63%). The ankle was the second most commonly affected joint (21 patients, 31%), followed by the knee (15 patients, 22%). In all, 14 patients had an additional lower-extremity joint affected. Upper-extremity involvement occurred in only nine patients.

Overall, about half (33) of patients had only one affected joint; 22 patients had two; 8 patients had three; and only 2 patients each had four or five.

In multivariate analysis, the authors reported that cancer surgery was performed on 60% of gout attack patients versus 34% of controls, a significant difference. “Cancers, especially hematologic malignancies, are known to cause hyperuricemia and gout because of high rates of cellular turnover,” wrote the investigators.

Presurgical serum uric acid levels greater than or equal to 9 mg/dL were also significantly correlated with an attack. This was “the most important risk factor,” and “the risk of attack increased in proportion to presurgical uric acid levels,” the added.

In an interview, Dr. Kenneth Saag, director of the center for education and research on therapeutics of musculoskeletal disorders at the University of Alabama at Birmingham, who was not affiliated with the study, said assessing a gout patient's presurgical urate levels isn't common practice, and shouldn't be. “Knowing the serum urate is only partially related to the likelihood of postsurgical gout. The level of serum urate is not something that can be managed in the perioperative period, anyway.”

A lack of colchicine prophylaxis before surgery was also tied to a significant risk of attack. But Dr. Saag, urged caution. “Some patients have kidney dysfunction, and colchicine is not an unequivocally safe medicine.”

“[Postsurgical gout attacks] can prolong the hospital stay. Surgeons aren't particularly eager to send patients home after surgery if they can't walk or are in severe pain. Sometimes gout can cause fevers which can be confused with postoperative infection,” said Dr. Saag. On the other hand, “the treatments for gout can compromise healing. Sometimes, if a steroid like prednisone is used to manage gout, that may impair wound healing.”

Dr. Lee said his team had no financial disclosures in relation to this study.

The risk for a postsurgical gout flare is greatest in patients with high presurgical serum urate levels, patients who've had cancer surgery, and in those who did not receive presurgical colchicine, according to a study.

Dr. Eun Bong Lee of the Seoul (South Korea) National University and colleagues looked at 67 patients who had a postsurgical gout attack and 67 who did not. All had prior histories of gout (Ann. Rheum. Dis. 2007 Nov. 12 [Epub doi:10.1136/ard.2007.078683]).

In an interview, Dr. Lee said “the postsurgical gout attack develops within 14 days after the surgery,” although the mean in this study was 4 days.

Lower extremity joints were affected in 65 of the 67 patients (97%) with a postsurgical gout flare. The most common site was the first metatarsophalangeal (MTP) joint (42 patients, or 63%). The ankle was the second most commonly affected joint (21 patients, 31%), followed by the knee (15 patients, 22%). In all, 14 patients had an additional lower-extremity joint affected. Upper-extremity involvement occurred in only nine patients.

Overall, about half (33) of patients had only one affected joint; 22 patients had two; 8 patients had three; and only 2 patients each had four or five.

In multivariate analysis, the authors reported that cancer surgery was performed on 60% of gout attack patients versus 34% of controls, a significant difference. “Cancers, especially hematologic malignancies, are known to cause hyperuricemia and gout because of high rates of cellular turnover,” wrote the investigators.

Presurgical serum uric acid levels greater than or equal to 9 mg/dL were also significantly correlated with an attack. This was “the most important risk factor,” and “the risk of attack increased in proportion to presurgical uric acid levels,” the added.

In an interview, Dr. Kenneth Saag, director of the center for education and research on therapeutics of musculoskeletal disorders at the University of Alabama at Birmingham, who was not affiliated with the study, said assessing a gout patient's presurgical urate levels isn't common practice, and shouldn't be. “Knowing the serum urate is only partially related to the likelihood of postsurgical gout. The level of serum urate is not something that can be managed in the perioperative period, anyway.”

A lack of colchicine prophylaxis before surgery was also tied to a significant risk of attack. But Dr. Saag, urged caution. “Some patients have kidney dysfunction, and colchicine is not an unequivocally safe medicine.”

“[Postsurgical gout attacks] can prolong the hospital stay. Surgeons aren't particularly eager to send patients home after surgery if they can't walk or are in severe pain. Sometimes gout can cause fevers which can be confused with postoperative infection,” said Dr. Saag. On the other hand, “the treatments for gout can compromise healing. Sometimes, if a steroid like prednisone is used to manage gout, that may impair wound healing.”

Dr. Lee said his team had no financial disclosures in relation to this study.

The risk for a postsurgical gout flare is greatest in patients with high presurgical serum urate levels, patients who've had cancer surgery, and in those who did not receive presurgical colchicine, according to a study.

Dr. Eun Bong Lee of the Seoul (South Korea) National University and colleagues looked at 67 patients who had a postsurgical gout attack and 67 who did not. All had prior histories of gout (Ann. Rheum. Dis. 2007 Nov. 12 [Epub doi:10.1136/ard.2007.078683]).

In an interview, Dr. Lee said “the postsurgical gout attack develops within 14 days after the surgery,” although the mean in this study was 4 days.

Lower extremity joints were affected in 65 of the 67 patients (97%) with a postsurgical gout flare. The most common site was the first metatarsophalangeal (MTP) joint (42 patients, or 63%). The ankle was the second most commonly affected joint (21 patients, 31%), followed by the knee (15 patients, 22%). In all, 14 patients had an additional lower-extremity joint affected. Upper-extremity involvement occurred in only nine patients.

Overall, about half (33) of patients had only one affected joint; 22 patients had two; 8 patients had three; and only 2 patients each had four or five.

In multivariate analysis, the authors reported that cancer surgery was performed on 60% of gout attack patients versus 34% of controls, a significant difference. “Cancers, especially hematologic malignancies, are known to cause hyperuricemia and gout because of high rates of cellular turnover,” wrote the investigators.

Presurgical serum uric acid levels greater than or equal to 9 mg/dL were also significantly correlated with an attack. This was “the most important risk factor,” and “the risk of attack increased in proportion to presurgical uric acid levels,” the added.

In an interview, Dr. Kenneth Saag, director of the center for education and research on therapeutics of musculoskeletal disorders at the University of Alabama at Birmingham, who was not affiliated with the study, said assessing a gout patient's presurgical urate levels isn't common practice, and shouldn't be. “Knowing the serum urate is only partially related to the likelihood of postsurgical gout. The level of serum urate is not something that can be managed in the perioperative period, anyway.”

A lack of colchicine prophylaxis before surgery was also tied to a significant risk of attack. But Dr. Saag, urged caution. “Some patients have kidney dysfunction, and colchicine is not an unequivocally safe medicine.”

“[Postsurgical gout attacks] can prolong the hospital stay. Surgeons aren't particularly eager to send patients home after surgery if they can't walk or are in severe pain. Sometimes gout can cause fevers which can be confused with postoperative infection,” said Dr. Saag. On the other hand, “the treatments for gout can compromise healing. Sometimes, if a steroid like prednisone is used to manage gout, that may impair wound healing.”

Dr. Lee said his team had no financial disclosures in relation to this study.

African American and Hispanic rheumatoid arthritis patients treated at public clinics wait longer to start disease-modifying antirheumatic drug therapy than do their white counterparts receiving care at private clinics.

Early intervention with DMARDs has been shown to delay joint damage.

Dr. Maria E. Suarez-Almazor, rheumatology section chief at the University of Texas M.D. Anderson Cancer Center, Houston, reported data from her retrospective cohort study of all medical records of new patients with a rheumatoid arthritis diagnosis seen at a public clinic (n=118) and a private clinic (n=167).

Both facilities are affiliated with the Baylor College of Medicine, Houston, staffed by Baylor rheumatology fellows and faculty, and considered tertiary-level care facilities. The public clinic cares for mostly minority, disadvantaged, or uninsured patients. Most of the private clinic patients had private insurance.

Socioeconomic status was inferred from insurance status and attendance at the public or private clinic, an admittedly imperfect method. Patients were classified as white, African American, Hispanic, or other. Nonwhites accounted for 83% of the patients seen in the public clinic versus 18% in the private clinic, a highly significant statistical difference.

The median time to initiation of DMARDs was 7 years for public clinic patients and 3 years for private clinic patients. The median time to initiation of steroids was 23 years for public patients and 1 year for private patients. And in all patients at both clinics, the median time to initiation of DMARDs for white patients was 3 years, versus 7 years for nonwhites (J. Rheumatol. 2007 Nov. 1 [Epub ahead of print]).

In an interview, Dr. Suarez-Almazor questioned whether the disparity is related to a communication problem between patients and doctors, such that physicians are unable to communicate the importance of expensive DMARDs.

She reported no conflicts of interest in relation to this study.

African American and Hispanic rheumatoid arthritis patients treated at public clinics wait longer to start disease-modifying antirheumatic drug therapy than do their white counterparts receiving care at private clinics.

Early intervention with DMARDs has been shown to delay joint damage.

Dr. Maria E. Suarez-Almazor, rheumatology section chief at the University of Texas M.D. Anderson Cancer Center, Houston, reported data from her retrospective cohort study of all medical records of new patients with a rheumatoid arthritis diagnosis seen at a public clinic (n=118) and a private clinic (n=167).

Both facilities are affiliated with the Baylor College of Medicine, Houston, staffed by Baylor rheumatology fellows and faculty, and considered tertiary-level care facilities. The public clinic cares for mostly minority, disadvantaged, or uninsured patients. Most of the private clinic patients had private insurance.

Socioeconomic status was inferred from insurance status and attendance at the public or private clinic, an admittedly imperfect method. Patients were classified as white, African American, Hispanic, or other. Nonwhites accounted for 83% of the patients seen in the public clinic versus 18% in the private clinic, a highly significant statistical difference.

The median time to initiation of DMARDs was 7 years for public clinic patients and 3 years for private clinic patients. The median time to initiation of steroids was 23 years for public patients and 1 year for private patients. And in all patients at both clinics, the median time to initiation of DMARDs for white patients was 3 years, versus 7 years for nonwhites (J. Rheumatol. 2007 Nov. 1 [Epub ahead of print]).

In an interview, Dr. Suarez-Almazor questioned whether the disparity is related to a communication problem between patients and doctors, such that physicians are unable to communicate the importance of expensive DMARDs.

She reported no conflicts of interest in relation to this study.

African American and Hispanic rheumatoid arthritis patients treated at public clinics wait longer to start disease-modifying antirheumatic drug therapy than do their white counterparts receiving care at private clinics.

Early intervention with DMARDs has been shown to delay joint damage.

Dr. Maria E. Suarez-Almazor, rheumatology section chief at the University of Texas M.D. Anderson Cancer Center, Houston, reported data from her retrospective cohort study of all medical records of new patients with a rheumatoid arthritis diagnosis seen at a public clinic (n=118) and a private clinic (n=167).

Both facilities are affiliated with the Baylor College of Medicine, Houston, staffed by Baylor rheumatology fellows and faculty, and considered tertiary-level care facilities. The public clinic cares for mostly minority, disadvantaged, or uninsured patients. Most of the private clinic patients had private insurance.

Socioeconomic status was inferred from insurance status and attendance at the public or private clinic, an admittedly imperfect method. Patients were classified as white, African American, Hispanic, or other. Nonwhites accounted for 83% of the patients seen in the public clinic versus 18% in the private clinic, a highly significant statistical difference.

The median time to initiation of DMARDs was 7 years for public clinic patients and 3 years for private clinic patients. The median time to initiation of steroids was 23 years for public patients and 1 year for private patients. And in all patients at both clinics, the median time to initiation of DMARDs for white patients was 3 years, versus 7 years for nonwhites (J. Rheumatol. 2007 Nov. 1 [Epub ahead of print]).

In an interview, Dr. Suarez-Almazor questioned whether the disparity is related to a communication problem between patients and doctors, such that physicians are unable to communicate the importance of expensive DMARDs.

She reported no conflicts of interest in relation to this study.

Rheumatoid arthritis patients have not experienced a decline in mortality, despite a dramatically increased life expectancy in the general population since the 1950s, according to investigators reporting on a cohort study.

In an interview, study investigator Dr. Hilal Maradit Kremers, of the Mayo Clinic in Rochester, Minn., said, “One assumes that since rheumatologists are trying to manage [RA] more aggressively, it must have a positive impact on mortality. … But all of our research is showing that the mortality in the RA patients did not change.”

In a population-based incidence cohort study, researchers looked at all 822 adult residents of Rochester in whom RA was first diagnosed between 1955 and 1995 and all adult residents of Olmsted County in whom RA was diagnosed between 1995 and 2000. The patients were followed up through medical records until their death or Jan. 1, 2007. The mean age at incidence was 58 years. Nearly three-quarters were women. The median length of follow-up was 11.7 years (Arthritis Rheum. 2007;56:3583–7).

RA patients' mortality was unchanged in each of the five study periods: from 1955 to 1964, 1965 to 1974, 1975 to 1984, 1985 to 1994, and 1995 to 2000. Female mortality hovered around 2.4 per 100 person-years, and male mortality was constant at about 2.5 per 100 person-years. In contrast, mortality in women in the Minnesota general population declined from 1.0 per 100 person-years in 1965 to 0.2 per 100 person-years in 2000. For men, the rate went from 1.2 to 0.3 per 100 person-years.

“Patients in whom RA was diagnosed in more recent years had a mortality rate similar to that of their peers in whom RA was diagnosed in the 1950s and 1960s. … The dramatic changes in therapeutic strategies for RA in the last 4–5 decades have not had a major impact on the excess mortality.”

Dr. Kremers reported no conflicts of interest in relation to this study.

Rheumatoid arthritis patients have not experienced a decline in mortality, despite a dramatically increased life expectancy in the general population since the 1950s, according to investigators reporting on a cohort study.

In an interview, study investigator Dr. Hilal Maradit Kremers, of the Mayo Clinic in Rochester, Minn., said, “One assumes that since rheumatologists are trying to manage [RA] more aggressively, it must have a positive impact on mortality. … But all of our research is showing that the mortality in the RA patients did not change.”

In a population-based incidence cohort study, researchers looked at all 822 adult residents of Rochester in whom RA was first diagnosed between 1955 and 1995 and all adult residents of Olmsted County in whom RA was diagnosed between 1995 and 2000. The patients were followed up through medical records until their death or Jan. 1, 2007. The mean age at incidence was 58 years. Nearly three-quarters were women. The median length of follow-up was 11.7 years (Arthritis Rheum. 2007;56:3583–7).

RA patients' mortality was unchanged in each of the five study periods: from 1955 to 1964, 1965 to 1974, 1975 to 1984, 1985 to 1994, and 1995 to 2000. Female mortality hovered around 2.4 per 100 person-years, and male mortality was constant at about 2.5 per 100 person-years. In contrast, mortality in women in the Minnesota general population declined from 1.0 per 100 person-years in 1965 to 0.2 per 100 person-years in 2000. For men, the rate went from 1.2 to 0.3 per 100 person-years.

“Patients in whom RA was diagnosed in more recent years had a mortality rate similar to that of their peers in whom RA was diagnosed in the 1950s and 1960s. … The dramatic changes in therapeutic strategies for RA in the last 4–5 decades have not had a major impact on the excess mortality.”

Dr. Kremers reported no conflicts of interest in relation to this study.

Rheumatoid arthritis patients have not experienced a decline in mortality, despite a dramatically increased life expectancy in the general population since the 1950s, according to investigators reporting on a cohort study.

In an interview, study investigator Dr. Hilal Maradit Kremers, of the Mayo Clinic in Rochester, Minn., said, “One assumes that since rheumatologists are trying to manage [RA] more aggressively, it must have a positive impact on mortality. … But all of our research is showing that the mortality in the RA patients did not change.”

In a population-based incidence cohort study, researchers looked at all 822 adult residents of Rochester in whom RA was first diagnosed between 1955 and 1995 and all adult residents of Olmsted County in whom RA was diagnosed between 1995 and 2000. The patients were followed up through medical records until their death or Jan. 1, 2007. The mean age at incidence was 58 years. Nearly three-quarters were women. The median length of follow-up was 11.7 years (Arthritis Rheum. 2007;56:3583–7).

RA patients' mortality was unchanged in each of the five study periods: from 1955 to 1964, 1965 to 1974, 1975 to 1984, 1985 to 1994, and 1995 to 2000. Female mortality hovered around 2.4 per 100 person-years, and male mortality was constant at about 2.5 per 100 person-years. In contrast, mortality in women in the Minnesota general population declined from 1.0 per 100 person-years in 1965 to 0.2 per 100 person-years in 2000. For men, the rate went from 1.2 to 0.3 per 100 person-years.

“Patients in whom RA was diagnosed in more recent years had a mortality rate similar to that of their peers in whom RA was diagnosed in the 1950s and 1960s. … The dramatic changes in therapeutic strategies for RA in the last 4–5 decades have not had a major impact on the excess mortality.”

Dr. Kremers reported no conflicts of interest in relation to this study.

The boy had back pain for more than a year. Neither physical therapy nor anti-inflammatory drugs had helped. He had no significant history of injury and no family history of lower back pain. He had no skin rashes, colitis, or other complaints. He previously had an MRI of his lumbar spine, which appeared normal, and a normal CT scan of his pelvis,

When he presented to a neurosurgeon, he had lower back pain and significant limitation of movement in his lumbar spine. An MRI of the sacroiliac revealed significant inflammation on both sides of the joint (see images), compatible with sacroiliitis, a finding highly suggestive of ankylosing spondylitis (AS). He was referred to Dr. Norman B. Gaylis, a rheumatologist in Miami.

Patients withAS tend to present with sacroiliitis, especially when they are human leukocyte antigen B27-positive. “Many patients with back pain have their diagnosis missed,” he said, because either physicians don't think of AS or the x-ray is negative. If an MRI is done, it is typically on the lumbar spine.

The differential diagnosis for lower back pain includes disk damage, trauma, or muscle strain, but sometimes patients are dismissed as imagining the pain.

Historically, diagnosis of AS has depended on the radiographic finding of sacroiliitis. “The findings on MRI [for AS], similar to those for rheumatoid arthritis, occur far earlier than you will see on x-ray,” said Dr. Gaylis. MRI findings of AS—synovitis and intense enhancing bone marrow edema/osteitis, as in this case—can precede x-ray evidence by 3 years (J. Rheumatol. 1999;26:1953–8).

MRIs show synovitis and intense enhancing bone marrow edema/osteitis.

The boy had back pain for more than a year. Neither physical therapy nor anti-inflammatory drugs had helped. He had no significant history of injury and no family history of lower back pain. He had no skin rashes, colitis, or other complaints. He previously had an MRI of his lumbar spine, which appeared normal, and a normal CT scan of his pelvis,

When he presented to a neurosurgeon, he had lower back pain and significant limitation of movement in his lumbar spine. An MRI of the sacroiliac revealed significant inflammation on both sides of the joint (see images), compatible with sacroiliitis, a finding highly suggestive of ankylosing spondylitis (AS). He was referred to Dr. Norman B. Gaylis, a rheumatologist in Miami.

Patients withAS tend to present with sacroiliitis, especially when they are human leukocyte antigen B27-positive. “Many patients with back pain have their diagnosis missed,” he said, because either physicians don't think of AS or the x-ray is negative. If an MRI is done, it is typically on the lumbar spine.

The differential diagnosis for lower back pain includes disk damage, trauma, or muscle strain, but sometimes patients are dismissed as imagining the pain.

Historically, diagnosis of AS has depended on the radiographic finding of sacroiliitis. “The findings on MRI [for AS], similar to those for rheumatoid arthritis, occur far earlier than you will see on x-ray,” said Dr. Gaylis. MRI findings of AS—synovitis and intense enhancing bone marrow edema/osteitis, as in this case—can precede x-ray evidence by 3 years (J. Rheumatol. 1999;26:1953–8).

MRIs show synovitis and intense enhancing bone marrow edema/osteitis.

The boy had back pain for more than a year. Neither physical therapy nor anti-inflammatory drugs had helped. He had no significant history of injury and no family history of lower back pain. He had no skin rashes, colitis, or other complaints. He previously had an MRI of his lumbar spine, which appeared normal, and a normal CT scan of his pelvis,

When he presented to a neurosurgeon, he had lower back pain and significant limitation of movement in his lumbar spine. An MRI of the sacroiliac revealed significant inflammation on both sides of the joint (see images), compatible with sacroiliitis, a finding highly suggestive of ankylosing spondylitis (AS). He was referred to Dr. Norman B. Gaylis, a rheumatologist in Miami.

Patients withAS tend to present with sacroiliitis, especially when they are human leukocyte antigen B27-positive. “Many patients with back pain have their diagnosis missed,” he said, because either physicians don't think of AS or the x-ray is negative. If an MRI is done, it is typically on the lumbar spine.

The differential diagnosis for lower back pain includes disk damage, trauma, or muscle strain, but sometimes patients are dismissed as imagining the pain.

Historically, diagnosis of AS has depended on the radiographic finding of sacroiliitis. “The findings on MRI [for AS], similar to those for rheumatoid arthritis, occur far earlier than you will see on x-ray,” said Dr. Gaylis. MRI findings of AS—synovitis and intense enhancing bone marrow edema/osteitis, as in this case—can precede x-ray evidence by 3 years (J. Rheumatol. 1999;26:1953–8).

MRIs show synovitis and intense enhancing bone marrow edema/osteitis.

BOSTON — Rheumatologists must rethink their reflex to prescribe methotrexate for psoriatic arthritis, given data showing anti-tumor necrosis factor agents are more effective for this indication, Dr. Christopher Ritchlin said at a rheumatology conference sponsored by Harvard Medical School.

“About 70%-80% of clinicians around the world who treat psoriatic arthritis say methotrexate is the first drug that they use, yet the only double-blind randomized controlled trial addressing the question was too underpowered and underdosed to make any conclusions regarding efficacy,” he added.

Another concern is liver toxicity with methotrexate, since psoriasis patients tend to have higher alcoholism rates. And there is evidence of progression of fibrosis in psoriatic arthritis patients on methotrexate, said Dr. Ritchlin, of the University of Rochester, N.Y. Also, unlike rheumatoid arthritis, there is no evidence that methotrexate is synergistic with other disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis.

In contrast, the production of TNF-α has been shown to play a central role in the development of psoriasis and psoriatic arthritis by sustaining the inflammatory process in the skin and the joints, and anti-TNF-α agents appear to effectively block that activity, said Dr. Ritchlin. Dr. Marte Schrumpf Heiberg of Diakonhjemmet Hospital, Oslo, has reported data from 526 patients with psoriatic arthritis. After 6 months, patients on anti-TNF-α treatment demonstrated significantly greater clinical improvement in disease measures, versus those on methotrexate monotherapy (Ann. Rheum. Dis. 2007;66:1038–42).

And Dr. Filip van den Bosch of University Hospital, in Gent (Belgium), and colleagues presented data showing adalimumab in 414 patients with psoriatic arthritis resulted in clinically meaningful joint and skin improvements at 12 weeks and was well tolerated. In a separate study, the researchers linked adalimumab with clinically important gains in psoriatic nail disease.

Anti-TNF-α therapy also seems to impact the enthesopathic pathology of psoriatic arthritis. Dr. Helena Marzo-Ortega of Chapel Allerton Hospital in Leeds (England), and colleagues have shown infliximab is tied to improvements in MRI-determined bone edema in psoriatic arthritis (Ann. Rheum. Dis. 2007;66:778–81).

Other potential therapeutic targets for psoriatic arthritis include B cells and T cells, as well as the interleukin-23/Th17 pathway, which is directly tied to psoriasis. Anti-p40 therapy targets an interleukin-23 subunit.

“Psoriatic arthritis, unlike rheumatoid arthritis, is quite complex in its disease manifestation,” Dr. Ritchlin. “Traditionally, psoriatic arthritis was defined as an inflammatory arthritis associated with psoriasis. More and more, however, it has become clear that psoriasis is a systemic disease.”

Anti-TNF-α agents come closest to achieving the goal of a treatment that is as simple and minimally toxic as possible, said Dr Ritchlin.

Anti-TNF-α agents come closest to achieving the goal of a treatment that is as simple and minimally toxic as possible. DR. RITCHLIN

BOSTON — Rheumatologists must rethink their reflex to prescribe methotrexate for psoriatic arthritis, given data showing anti-tumor necrosis factor agents are more effective for this indication, Dr. Christopher Ritchlin said at a rheumatology conference sponsored by Harvard Medical School.

“About 70%-80% of clinicians around the world who treat psoriatic arthritis say methotrexate is the first drug that they use, yet the only double-blind randomized controlled trial addressing the question was too underpowered and underdosed to make any conclusions regarding efficacy,” he added.

Another concern is liver toxicity with methotrexate, since psoriasis patients tend to have higher alcoholism rates. And there is evidence of progression of fibrosis in psoriatic arthritis patients on methotrexate, said Dr. Ritchlin, of the University of Rochester, N.Y. Also, unlike rheumatoid arthritis, there is no evidence that methotrexate is synergistic with other disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis.

In contrast, the production of TNF-α has been shown to play a central role in the development of psoriasis and psoriatic arthritis by sustaining the inflammatory process in the skin and the joints, and anti-TNF-α agents appear to effectively block that activity, said Dr. Ritchlin. Dr. Marte Schrumpf Heiberg of Diakonhjemmet Hospital, Oslo, has reported data from 526 patients with psoriatic arthritis. After 6 months, patients on anti-TNF-α treatment demonstrated significantly greater clinical improvement in disease measures, versus those on methotrexate monotherapy (Ann. Rheum. Dis. 2007;66:1038–42).

And Dr. Filip van den Bosch of University Hospital, in Gent (Belgium), and colleagues presented data showing adalimumab in 414 patients with psoriatic arthritis resulted in clinically meaningful joint and skin improvements at 12 weeks and was well tolerated. In a separate study, the researchers linked adalimumab with clinically important gains in psoriatic nail disease.

Anti-TNF-α therapy also seems to impact the enthesopathic pathology of psoriatic arthritis. Dr. Helena Marzo-Ortega of Chapel Allerton Hospital in Leeds (England), and colleagues have shown infliximab is tied to improvements in MRI-determined bone edema in psoriatic arthritis (Ann. Rheum. Dis. 2007;66:778–81).

Other potential therapeutic targets for psoriatic arthritis include B cells and T cells, as well as the interleukin-23/Th17 pathway, which is directly tied to psoriasis. Anti-p40 therapy targets an interleukin-23 subunit.

“Psoriatic arthritis, unlike rheumatoid arthritis, is quite complex in its disease manifestation,” Dr. Ritchlin. “Traditionally, psoriatic arthritis was defined as an inflammatory arthritis associated with psoriasis. More and more, however, it has become clear that psoriasis is a systemic disease.”

Anti-TNF-α agents come closest to achieving the goal of a treatment that is as simple and minimally toxic as possible, said Dr Ritchlin.

Anti-TNF-α agents come closest to achieving the goal of a treatment that is as simple and minimally toxic as possible. DR. RITCHLIN

BOSTON — Rheumatologists must rethink their reflex to prescribe methotrexate for psoriatic arthritis, given data showing anti-tumor necrosis factor agents are more effective for this indication, Dr. Christopher Ritchlin said at a rheumatology conference sponsored by Harvard Medical School.

“About 70%-80% of clinicians around the world who treat psoriatic arthritis say methotrexate is the first drug that they use, yet the only double-blind randomized controlled trial addressing the question was too underpowered and underdosed to make any conclusions regarding efficacy,” he added.

Another concern is liver toxicity with methotrexate, since psoriasis patients tend to have higher alcoholism rates. And there is evidence of progression of fibrosis in psoriatic arthritis patients on methotrexate, said Dr. Ritchlin, of the University of Rochester, N.Y. Also, unlike rheumatoid arthritis, there is no evidence that methotrexate is synergistic with other disease-modifying antirheumatic drugs (DMARDs) in psoriatic arthritis.

In contrast, the production of TNF-α has been shown to play a central role in the development of psoriasis and psoriatic arthritis by sustaining the inflammatory process in the skin and the joints, and anti-TNF-α agents appear to effectively block that activity, said Dr. Ritchlin. Dr. Marte Schrumpf Heiberg of Diakonhjemmet Hospital, Oslo, has reported data from 526 patients with psoriatic arthritis. After 6 months, patients on anti-TNF-α treatment demonstrated significantly greater clinical improvement in disease measures, versus those on methotrexate monotherapy (Ann. Rheum. Dis. 2007;66:1038–42).

And Dr. Filip van den Bosch of University Hospital, in Gent (Belgium), and colleagues presented data showing adalimumab in 414 patients with psoriatic arthritis resulted in clinically meaningful joint and skin improvements at 12 weeks and was well tolerated. In a separate study, the researchers linked adalimumab with clinically important gains in psoriatic nail disease.

Anti-TNF-α therapy also seems to impact the enthesopathic pathology of psoriatic arthritis. Dr. Helena Marzo-Ortega of Chapel Allerton Hospital in Leeds (England), and colleagues have shown infliximab is tied to improvements in MRI-determined bone edema in psoriatic arthritis (Ann. Rheum. Dis. 2007;66:778–81).

Other potential therapeutic targets for psoriatic arthritis include B cells and T cells, as well as the interleukin-23/Th17 pathway, which is directly tied to psoriasis. Anti-p40 therapy targets an interleukin-23 subunit.

“Psoriatic arthritis, unlike rheumatoid arthritis, is quite complex in its disease manifestation,” Dr. Ritchlin. “Traditionally, psoriatic arthritis was defined as an inflammatory arthritis associated with psoriasis. More and more, however, it has become clear that psoriasis is a systemic disease.”

Anti-TNF-α agents come closest to achieving the goal of a treatment that is as simple and minimally toxic as possible, said Dr Ritchlin.

Anti-TNF-α agents come closest to achieving the goal of a treatment that is as simple and minimally toxic as possible. DR. RITCHLIN

True acupuncture and sham acupuncture both were much more effective against chronic low-back pain than was conventional treatment in a large clinical trial comparing the three approaches.

Almost half the subjects who received real or sham acupuncture for 6 months showed clinically relevant improvement in pain intensity or back-specific disability, versus one-fourth of the subjects who received a variety of conventional therapies, investigators in the German Acupuncture (GERAC) Trials reported. (See box.)

“To our knowledge, [this] study is the largest and most rigorous trial to investigate the efficacy of verum acupuncture for chronic low-back pain compared with sham acupuncture and guideline-based conventional therapy. The study yielded several surprising results,” said Dr. Michael Haake of the University of Regensburg, Bad Abbach, Germany, and his associates.

The study subjects were 1,162 adults with chronic low-back pain who were randomized to conventional treatment or real or sham acupuncture administered by physicians at 340 outpatient practices. The study physicians belonged to various medical specialties, had at least 140 hours of acupuncture training, and had practiced acupuncture for a median of 8 years.

Both types of acupuncture involved at least ten 30-minute sessions, usually twice per week, plus additional sessions if the subjects experienced a 10%–50% reduction in pain intensity. The two treatments were identical, except that the sham procedure avoided all known acupuncture points or meridians and involved only superficial insertion of the needles, without any manual stimulation. Subjects were unable to distinguish any difference.

Conventional therapies included at least 10 30-minute sessions with a physician or physiotherapist. Treating physicians were free to administer any combination of techniques, including physiotherapy, massage, heat therapy, electrotherapy, injections, analgesics, anti-inflammatory agents, yoga, hydrojet treatment, exercise, and patient education about managing back pain.

True acupuncture and sham acupuncture were found to be equally effective, as well as more effective than conventional therapies, in relieving pain, improving function, and improving quality of life. All the improvements were significant and persisted long after treatment was completed.

“While all randomized trials and meta-analyses to date have failed to show a clear advantage of acupuncture over conventional therapy for chronic low-back pain, our findings demonstrate significant superiority,” the investigators said (Arch. Intern. Med. 2007;167:1892–8).

Largely on the basis of these results, the German Federal Joint Committee of Physicians and Health Insurance Plans—an agency like the U.S. National Institutes of Health—made acupuncture for low-back pain an insured benefit in that country.

The investigators' finding “forces us to question the underlying action mechanism of acupuncture and to ask whether the emphasis placed on learning the traditional Chinese acupuncture points may be superfluous,” Dr. Haake added.

“The superiority of both forms of acupuncture suggests a common underlying mechanism that may act on pain generation, transmission of pain signals, or processing of pain signals by the central nervous system and that is stronger than the action mechanism of conventional therapy,” they said.

ELSEVIER GLOBAL MEDICAL NEWS

True acupuncture and sham acupuncture both were much more effective against chronic low-back pain than was conventional treatment in a large clinical trial comparing the three approaches.

Almost half the subjects who received real or sham acupuncture for 6 months showed clinically relevant improvement in pain intensity or back-specific disability, versus one-fourth of the subjects who received a variety of conventional therapies, investigators in the German Acupuncture (GERAC) Trials reported. (See box.)

“To our knowledge, [this] study is the largest and most rigorous trial to investigate the efficacy of verum acupuncture for chronic low-back pain compared with sham acupuncture and guideline-based conventional therapy. The study yielded several surprising results,” said Dr. Michael Haake of the University of Regensburg, Bad Abbach, Germany, and his associates.

The study subjects were 1,162 adults with chronic low-back pain who were randomized to conventional treatment or real or sham acupuncture administered by physicians at 340 outpatient practices. The study physicians belonged to various medical specialties, had at least 140 hours of acupuncture training, and had practiced acupuncture for a median of 8 years.

Both types of acupuncture involved at least ten 30-minute sessions, usually twice per week, plus additional sessions if the subjects experienced a 10%–50% reduction in pain intensity. The two treatments were identical, except that the sham procedure avoided all known acupuncture points or meridians and involved only superficial insertion of the needles, without any manual stimulation. Subjects were unable to distinguish any difference.

Conventional therapies included at least 10 30-minute sessions with a physician or physiotherapist. Treating physicians were free to administer any combination of techniques, including physiotherapy, massage, heat therapy, electrotherapy, injections, analgesics, anti-inflammatory agents, yoga, hydrojet treatment, exercise, and patient education about managing back pain.

True acupuncture and sham acupuncture were found to be equally effective, as well as more effective than conventional therapies, in relieving pain, improving function, and improving quality of life. All the improvements were significant and persisted long after treatment was completed.

“While all randomized trials and meta-analyses to date have failed to show a clear advantage of acupuncture over conventional therapy for chronic low-back pain, our findings demonstrate significant superiority,” the investigators said (Arch. Intern. Med. 2007;167:1892–8).

Largely on the basis of these results, the German Federal Joint Committee of Physicians and Health Insurance Plans—an agency like the U.S. National Institutes of Health—made acupuncture for low-back pain an insured benefit in that country.

The investigators' finding “forces us to question the underlying action mechanism of acupuncture and to ask whether the emphasis placed on learning the traditional Chinese acupuncture points may be superfluous,” Dr. Haake added.

“The superiority of both forms of acupuncture suggests a common underlying mechanism that may act on pain generation, transmission of pain signals, or processing of pain signals by the central nervous system and that is stronger than the action mechanism of conventional therapy,” they said.

ELSEVIER GLOBAL MEDICAL NEWS

True acupuncture and sham acupuncture both were much more effective against chronic low-back pain than was conventional treatment in a large clinical trial comparing the three approaches.

Almost half the subjects who received real or sham acupuncture for 6 months showed clinically relevant improvement in pain intensity or back-specific disability, versus one-fourth of the subjects who received a variety of conventional therapies, investigators in the German Acupuncture (GERAC) Trials reported. (See box.)

“To our knowledge, [this] study is the largest and most rigorous trial to investigate the efficacy of verum acupuncture for chronic low-back pain compared with sham acupuncture and guideline-based conventional therapy. The study yielded several surprising results,” said Dr. Michael Haake of the University of Regensburg, Bad Abbach, Germany, and his associates.

The study subjects were 1,162 adults with chronic low-back pain who were randomized to conventional treatment or real or sham acupuncture administered by physicians at 340 outpatient practices. The study physicians belonged to various medical specialties, had at least 140 hours of acupuncture training, and had practiced acupuncture for a median of 8 years.

Both types of acupuncture involved at least ten 30-minute sessions, usually twice per week, plus additional sessions if the subjects experienced a 10%–50% reduction in pain intensity. The two treatments were identical, except that the sham procedure avoided all known acupuncture points or meridians and involved only superficial insertion of the needles, without any manual stimulation. Subjects were unable to distinguish any difference.

Conventional therapies included at least 10 30-minute sessions with a physician or physiotherapist. Treating physicians were free to administer any combination of techniques, including physiotherapy, massage, heat therapy, electrotherapy, injections, analgesics, anti-inflammatory agents, yoga, hydrojet treatment, exercise, and patient education about managing back pain.

True acupuncture and sham acupuncture were found to be equally effective, as well as more effective than conventional therapies, in relieving pain, improving function, and improving quality of life. All the improvements were significant and persisted long after treatment was completed.

“While all randomized trials and meta-analyses to date have failed to show a clear advantage of acupuncture over conventional therapy for chronic low-back pain, our findings demonstrate significant superiority,” the investigators said (Arch. Intern. Med. 2007;167:1892–8).

Largely on the basis of these results, the German Federal Joint Committee of Physicians and Health Insurance Plans—an agency like the U.S. National Institutes of Health—made acupuncture for low-back pain an insured benefit in that country.

The investigators' finding “forces us to question the underlying action mechanism of acupuncture and to ask whether the emphasis placed on learning the traditional Chinese acupuncture points may be superfluous,” Dr. Haake added.

“The superiority of both forms of acupuncture suggests a common underlying mechanism that may act on pain generation, transmission of pain signals, or processing of pain signals by the central nervous system and that is stronger than the action mechanism of conventional therapy,” they said.

ELSEVIER GLOBAL MEDICAL NEWS

A genomewide association study of osteoarthritis susceptibility has begun in the United Kingdom with 8,000 patients and 6,000 controls, the largest study of its kind ever undertaken.

Dr. John Loughlin, principal investigator of the study and a geneticist at the Nuffield Department for Orthopaedic Surgery at the University of Oxford (England), said the study's massive size would provide it with “unprecedented power.”

The results will be made freely available to the public upon the study's completion.

In an interview, Dr. Loughlin explained that the study, known as arcOGEN (“arc” stands for Arthritis Research Campaign, who is funding the story; the “O” for osteoarthritis; and the “GEN” for genetics), will genotype only U.K. citizens of white British ancestry. He said his group already has 4,000 cases and is collecting another 4,000. “The controls are those genotyped as part of other studies,” he said.

The inclusion criterion for cases is a diagnosis of severe primary osteoarthritis (OA). “The vast majority of our cases [more than 75%] will have undergone arthroplasty of a hip or of a knee,” he said. There will be no inclusions or exclusions related to past or present drug treatment.

Dr. Loughlin hopes to have the first 4,000 cases genotyped by the summer of 2008 and the second 4,000 genotyped by the summer of 2009, with analyses performed by the autumn of 2009.

Dr. Roy Altman, visiting professor in the division of rheumatology at the University of California, Los Angeles, said “it's a little bit early to say what the clinical relevance [of this study] is going to be. … Unless you put in formulas for, for example, … whether the cases play soccer or not,” it will be difficult to tell how great is the effect of environmental factors like trauma on genetically predisposed OA candidates.

In addition, Dr. Altman, who is not affiliated with the study, pointed out the study will be limited by the fact that it will look only at white British subjects. However, regarding Dr. Loughlin's suitability to undertake such research, he added: “You can't get anybody better than [Dr. Loughlin]. He is the best of the osteoarthritis geneticists, and I know he will do a very credible job.”

Several genes have already been found to be associated with susceptibility to OA. “The most compelling so far are FRZB, GDF5, and ASPN,” said Dr. Loughlin. “Intriguingly, all encode proteins that are involved in cell-signaling pathways in the tissues of the articulating joint, implying that OA susceptibility may partly be accounted for by aberrant cell signals. This is exciting, as these are potentially modifiable.” He added, however, that although several studies have been published on OA genetic susceptibility, few have been replicated.

Dr. Loughlin and his associates hope to find 10–20 of the genes that confer a strong to moderate risk for OA.

Large, genomewide studies like arcOGEN (versus smaller, linkage region-focused studies) will likely become more common as the cost of these studies continues to drop, Dr. Loughlin said. “Focusing on particular candidates will happen when a [genomewide association study] has highlighted a particular genomic region as likely to harbor susceptibility genes.”

Dr. Altman said, “The technology of identifying genes has advanced so much that now we can do these kind of genomewide studies in bulk, with 8,000 patients, that we couldn't have done 3 years ago. … I'm not quite sure how it's going to apply [to clinical practice], but it's certainly something that's important. If you find genetic predispositions and you have a way of altering those genes, then it may be relevant.”

The £2.2 million grant from the Arthritis Research Campaign funding this study is the biggest ever given by the group, which says it is the fourth-largest medical research charity in the United Kingdom.

The arcOGEN study will be undertaken across eight centers in the United Kingdom Dr. Loughlin reported no conflicts of interest for himself or his associates.

'The technology of identifying genes has advanced so much that now we can do these kind of genomewide studies in bulk.' DR. ALTMAN

A genomewide association study of osteoarthritis susceptibility has begun in the United Kingdom with 8,000 patients and 6,000 controls, the largest study of its kind ever undertaken.

Dr. John Loughlin, principal investigator of the study and a geneticist at the Nuffield Department for Orthopaedic Surgery at the University of Oxford (England), said the study's massive size would provide it with “unprecedented power.”

The results will be made freely available to the public upon the study's completion.

In an interview, Dr. Loughlin explained that the study, known as arcOGEN (“arc” stands for Arthritis Research Campaign, who is funding the story; the “O” for osteoarthritis; and the “GEN” for genetics), will genotype only U.K. citizens of white British ancestry. He said his group already has 4,000 cases and is collecting another 4,000. “The controls are those genotyped as part of other studies,” he said.

The inclusion criterion for cases is a diagnosis of severe primary osteoarthritis (OA). “The vast majority of our cases [more than 75%] will have undergone arthroplasty of a hip or of a knee,” he said. There will be no inclusions or exclusions related to past or present drug treatment.

Dr. Loughlin hopes to have the first 4,000 cases genotyped by the summer of 2008 and the second 4,000 genotyped by the summer of 2009, with analyses performed by the autumn of 2009.

Dr. Roy Altman, visiting professor in the division of rheumatology at the University of California, Los Angeles, said “it's a little bit early to say what the clinical relevance [of this study] is going to be. … Unless you put in formulas for, for example, … whether the cases play soccer or not,” it will be difficult to tell how great is the effect of environmental factors like trauma on genetically predisposed OA candidates.

In addition, Dr. Altman, who is not affiliated with the study, pointed out the study will be limited by the fact that it will look only at white British subjects. However, regarding Dr. Loughlin's suitability to undertake such research, he added: “You can't get anybody better than [Dr. Loughlin]. He is the best of the osteoarthritis geneticists, and I know he will do a very credible job.”

Several genes have already been found to be associated with susceptibility to OA. “The most compelling so far are FRZB, GDF5, and ASPN,” said Dr. Loughlin. “Intriguingly, all encode proteins that are involved in cell-signaling pathways in the tissues of the articulating joint, implying that OA susceptibility may partly be accounted for by aberrant cell signals. This is exciting, as these are potentially modifiable.” He added, however, that although several studies have been published on OA genetic susceptibility, few have been replicated.

Dr. Loughlin and his associates hope to find 10–20 of the genes that confer a strong to moderate risk for OA.

Large, genomewide studies like arcOGEN (versus smaller, linkage region-focused studies) will likely become more common as the cost of these studies continues to drop, Dr. Loughlin said. “Focusing on particular candidates will happen when a [genomewide association study] has highlighted a particular genomic region as likely to harbor susceptibility genes.”

Dr. Altman said, “The technology of identifying genes has advanced so much that now we can do these kind of genomewide studies in bulk, with 8,000 patients, that we couldn't have done 3 years ago. … I'm not quite sure how it's going to apply [to clinical practice], but it's certainly something that's important. If you find genetic predispositions and you have a way of altering those genes, then it may be relevant.”

The £2.2 million grant from the Arthritis Research Campaign funding this study is the biggest ever given by the group, which says it is the fourth-largest medical research charity in the United Kingdom.

The arcOGEN study will be undertaken across eight centers in the United Kingdom Dr. Loughlin reported no conflicts of interest for himself or his associates.

'The technology of identifying genes has advanced so much that now we can do these kind of genomewide studies in bulk.' DR. ALTMAN

A genomewide association study of osteoarthritis susceptibility has begun in the United Kingdom with 8,000 patients and 6,000 controls, the largest study of its kind ever undertaken.

Dr. John Loughlin, principal investigator of the study and a geneticist at the Nuffield Department for Orthopaedic Surgery at the University of Oxford (England), said the study's massive size would provide it with “unprecedented power.”

The results will be made freely available to the public upon the study's completion.

In an interview, Dr. Loughlin explained that the study, known as arcOGEN (“arc” stands for Arthritis Research Campaign, who is funding the story; the “O” for osteoarthritis; and the “GEN” for genetics), will genotype only U.K. citizens of white British ancestry. He said his group already has 4,000 cases and is collecting another 4,000. “The controls are those genotyped as part of other studies,” he said.

The inclusion criterion for cases is a diagnosis of severe primary osteoarthritis (OA). “The vast majority of our cases [more than 75%] will have undergone arthroplasty of a hip or of a knee,” he said. There will be no inclusions or exclusions related to past or present drug treatment.

Dr. Loughlin hopes to have the first 4,000 cases genotyped by the summer of 2008 and the second 4,000 genotyped by the summer of 2009, with analyses performed by the autumn of 2009.

Dr. Roy Altman, visiting professor in the division of rheumatology at the University of California, Los Angeles, said “it's a little bit early to say what the clinical relevance [of this study] is going to be. … Unless you put in formulas for, for example, … whether the cases play soccer or not,” it will be difficult to tell how great is the effect of environmental factors like trauma on genetically predisposed OA candidates.

In addition, Dr. Altman, who is not affiliated with the study, pointed out the study will be limited by the fact that it will look only at white British subjects. However, regarding Dr. Loughlin's suitability to undertake such research, he added: “You can't get anybody better than [Dr. Loughlin]. He is the best of the osteoarthritis geneticists, and I know he will do a very credible job.”

Several genes have already been found to be associated with susceptibility to OA. “The most compelling so far are FRZB, GDF5, and ASPN,” said Dr. Loughlin. “Intriguingly, all encode proteins that are involved in cell-signaling pathways in the tissues of the articulating joint, implying that OA susceptibility may partly be accounted for by aberrant cell signals. This is exciting, as these are potentially modifiable.” He added, however, that although several studies have been published on OA genetic susceptibility, few have been replicated.

Dr. Loughlin and his associates hope to find 10–20 of the genes that confer a strong to moderate risk for OA.

Large, genomewide studies like arcOGEN (versus smaller, linkage region-focused studies) will likely become more common as the cost of these studies continues to drop, Dr. Loughlin said. “Focusing on particular candidates will happen when a [genomewide association study] has highlighted a particular genomic region as likely to harbor susceptibility genes.”

Dr. Altman said, “The technology of identifying genes has advanced so much that now we can do these kind of genomewide studies in bulk, with 8,000 patients, that we couldn't have done 3 years ago. … I'm not quite sure how it's going to apply [to clinical practice], but it's certainly something that's important. If you find genetic predispositions and you have a way of altering those genes, then it may be relevant.”

The £2.2 million grant from the Arthritis Research Campaign funding this study is the biggest ever given by the group, which says it is the fourth-largest medical research charity in the United Kingdom.

The arcOGEN study will be undertaken across eight centers in the United Kingdom Dr. Loughlin reported no conflicts of interest for himself or his associates.

'The technology of identifying genes has advanced so much that now we can do these kind of genomewide studies in bulk.' DR. ALTMAN

Adding a proton pump inhibitor to a nonsteroidal anti-inflammatory drug provides as much protection against NSAID-induced gastropathy as a cyclooxygenase-2 inhibitor (coxib), according to a new study September 2007 issue of the journal Gastroenterology.

Adding a proton pump inhibitor (PPI) to a coxib may provide some additional protection, but in recent years some coxibs have been shown to cause serious cardiovascular disease, wrote Wayne A. Ray, Ph.D., and his colleagues at Vanderbilt University, Nashville, Tenn.

The observational study used data from TennCare, the state of Tennessee's Medicaid program. Patients aged 40 years and older with a new episode of prescribed NSAID or coxib use between 1996 and 2004 were included. After excluding patients with serious illnesses such as cancer, HIV infection, cirrhosis, and chronic alcoholism, and those with less than 2 years of baseline data, the study included 234,010 new episodes of NSAID use and 48,710 new episodes of coxib use, with a total of 363,037 person-years of follow-up.

The investigators adjusted for a large number of demographic variables; prior history of peptic ulcer disease; use of low-dose aspirin, other antiplatelet drugs, anticoagulants, or systemic corticosteroids; new residence in a nursing home; and new nongastrointestinal hospital admission.

They found that the use of NSAIDs without gastroprotective cotherapy was associated with 5.65 peptic ulcer hospitalizations per 1,000 person-years, which is 2.8 times the incidence for comparable patients who were former users of either NSAIDs or coxibs.

Use of a PPI, a double-dose histamine-2 receptor antagonist, or misoprostol along with an NSAID reduced the risk of peptic ulcer hospitalization by 39%. Of the various gastroprotective therapies, PPIs were associated with the greatest risk reduction—54%—among NSAID users.

Unprotected use of a coxib resulted in a 40% reduction in the risk of peptic ulcer hospitalization, compared with unprotected use of an NSAID. Using a gastroprotective therapy in addition to a coxib resulted in a further 10% reduction in risk (for a total of 50%), with no statistically significant advantage for PPIs over other gastroprotective therapies.

In a subanalysis adjusted for dose, naproxen proved to be associated with the highest risk of peptic ulcer hospitalization, with an adjusted rate of 7.8 per 1,000 patient-years. Ibuprofen, rofecoxib, and celecoxib all were associated with significantly lower risks of hospitalization.

Another subgroup analysis showed that an NSAID with gastroprotection was significantly better for several patient groups than an NSAID alone. These groups included patients over the age of 65 years and those with a history of previous ulcers.

In other subgroups with medical comorbidities, those taking low-dose aspirin, and those on antiplatelet or anticoagulant therapy, gastroprotection had no statistically significant improvement over unprotected NSAIDs. The researchers said this was partly because of relatively small numbers of patients in some of the subgroups.

The study was supported by the Agency for Healthcare Research and Quality, and the investigators stated that they received no support from any pharmaceutical company. “[It] is increasingly unlikely that large clinical trials of gastroprotective cotherapy in NSAID users will be conducted,” they wrote. “Proton pump inhibitors are available generically, which limits the incentives for pharmaceutical manufacturers to fund such studies. Furthermore, because NSAID-induced gastropathy is frequent and potentially life threatening, the ethics of randomizing patients to NSAID use without gastroprotective cotherapy are questionable.”

The researchers recommended future trials directly comparing coxibs to NSAIDs with a PPI, and said additional investigation is “urgently needed” to study the benefits of adding a PPI to celecoxib and other coxibs.

Adding a proton pump inhibitor to a nonsteroidal anti-inflammatory drug provides as much protection against NSAID-induced gastropathy as a cyclooxygenase-2 inhibitor (coxib), according to a new study September 2007 issue of the journal Gastroenterology.

Adding a proton pump inhibitor (PPI) to a coxib may provide some additional protection, but in recent years some coxibs have been shown to cause serious cardiovascular disease, wrote Wayne A. Ray, Ph.D., and his colleagues at Vanderbilt University, Nashville, Tenn.

The observational study used data from TennCare, the state of Tennessee's Medicaid program. Patients aged 40 years and older with a new episode of prescribed NSAID or coxib use between 1996 and 2004 were included. After excluding patients with serious illnesses such as cancer, HIV infection, cirrhosis, and chronic alcoholism, and those with less than 2 years of baseline data, the study included 234,010 new episodes of NSAID use and 48,710 new episodes of coxib use, with a total of 363,037 person-years of follow-up.

The investigators adjusted for a large number of demographic variables; prior history of peptic ulcer disease; use of low-dose aspirin, other antiplatelet drugs, anticoagulants, or systemic corticosteroids; new residence in a nursing home; and new nongastrointestinal hospital admission.

They found that the use of NSAIDs without gastroprotective cotherapy was associated with 5.65 peptic ulcer hospitalizations per 1,000 person-years, which is 2.8 times the incidence for comparable patients who were former users of either NSAIDs or coxibs.

Use of a PPI, a double-dose histamine-2 receptor antagonist, or misoprostol along with an NSAID reduced the risk of peptic ulcer hospitalization by 39%. Of the various gastroprotective therapies, PPIs were associated with the greatest risk reduction—54%—among NSAID users.

Unprotected use of a coxib resulted in a 40% reduction in the risk of peptic ulcer hospitalization, compared with unprotected use of an NSAID. Using a gastroprotective therapy in addition to a coxib resulted in a further 10% reduction in risk (for a total of 50%), with no statistically significant advantage for PPIs over other gastroprotective therapies.

In a subanalysis adjusted for dose, naproxen proved to be associated with the highest risk of peptic ulcer hospitalization, with an adjusted rate of 7.8 per 1,000 patient-years. Ibuprofen, rofecoxib, and celecoxib all were associated with significantly lower risks of hospitalization.

Another subgroup analysis showed that an NSAID with gastroprotection was significantly better for several patient groups than an NSAID alone. These groups included patients over the age of 65 years and those with a history of previous ulcers.

In other subgroups with medical comorbidities, those taking low-dose aspirin, and those on antiplatelet or anticoagulant therapy, gastroprotection had no statistically significant improvement over unprotected NSAIDs. The researchers said this was partly because of relatively small numbers of patients in some of the subgroups.

The study was supported by the Agency for Healthcare Research and Quality, and the investigators stated that they received no support from any pharmaceutical company. “[It] is increasingly unlikely that large clinical trials of gastroprotective cotherapy in NSAID users will be conducted,” they wrote. “Proton pump inhibitors are available generically, which limits the incentives for pharmaceutical manufacturers to fund such studies. Furthermore, because NSAID-induced gastropathy is frequent and potentially life threatening, the ethics of randomizing patients to NSAID use without gastroprotective cotherapy are questionable.”

The researchers recommended future trials directly comparing coxibs to NSAIDs with a PPI, and said additional investigation is “urgently needed” to study the benefits of adding a PPI to celecoxib and other coxibs.

Adding a proton pump inhibitor to a nonsteroidal anti-inflammatory drug provides as much protection against NSAID-induced gastropathy as a cyclooxygenase-2 inhibitor (coxib), according to a new study September 2007 issue of the journal Gastroenterology.

Adding a proton pump inhibitor (PPI) to a coxib may provide some additional protection, but in recent years some coxibs have been shown to cause serious cardiovascular disease, wrote Wayne A. Ray, Ph.D., and his colleagues at Vanderbilt University, Nashville, Tenn.

The observational study used data from TennCare, the state of Tennessee's Medicaid program. Patients aged 40 years and older with a new episode of prescribed NSAID or coxib use between 1996 and 2004 were included. After excluding patients with serious illnesses such as cancer, HIV infection, cirrhosis, and chronic alcoholism, and those with less than 2 years of baseline data, the study included 234,010 new episodes of NSAID use and 48,710 new episodes of coxib use, with a total of 363,037 person-years of follow-up.

The investigators adjusted for a large number of demographic variables; prior history of peptic ulcer disease; use of low-dose aspirin, other antiplatelet drugs, anticoagulants, or systemic corticosteroids; new residence in a nursing home; and new nongastrointestinal hospital admission.

They found that the use of NSAIDs without gastroprotective cotherapy was associated with 5.65 peptic ulcer hospitalizations per 1,000 person-years, which is 2.8 times the incidence for comparable patients who were former users of either NSAIDs or coxibs.

Use of a PPI, a double-dose histamine-2 receptor antagonist, or misoprostol along with an NSAID reduced the risk of peptic ulcer hospitalization by 39%. Of the various gastroprotective therapies, PPIs were associated with the greatest risk reduction—54%—among NSAID users.

Unprotected use of a coxib resulted in a 40% reduction in the risk of peptic ulcer hospitalization, compared with unprotected use of an NSAID. Using a gastroprotective therapy in addition to a coxib resulted in a further 10% reduction in risk (for a total of 50%), with no statistically significant advantage for PPIs over other gastroprotective therapies.

In a subanalysis adjusted for dose, naproxen proved to be associated with the highest risk of peptic ulcer hospitalization, with an adjusted rate of 7.8 per 1,000 patient-years. Ibuprofen, rofecoxib, and celecoxib all were associated with significantly lower risks of hospitalization.

Another subgroup analysis showed that an NSAID with gastroprotection was significantly better for several patient groups than an NSAID alone. These groups included patients over the age of 65 years and those with a history of previous ulcers.

In other subgroups with medical comorbidities, those taking low-dose aspirin, and those on antiplatelet or anticoagulant therapy, gastroprotection had no statistically significant improvement over unprotected NSAIDs. The researchers said this was partly because of relatively small numbers of patients in some of the subgroups.

The study was supported by the Agency for Healthcare Research and Quality, and the investigators stated that they received no support from any pharmaceutical company. “[It] is increasingly unlikely that large clinical trials of gastroprotective cotherapy in NSAID users will be conducted,” they wrote. “Proton pump inhibitors are available generically, which limits the incentives for pharmaceutical manufacturers to fund such studies. Furthermore, because NSAID-induced gastropathy is frequent and potentially life threatening, the ethics of randomizing patients to NSAID use without gastroprotective cotherapy are questionable.”

The researchers recommended future trials directly comparing coxibs to NSAIDs with a PPI, and said additional investigation is “urgently needed” to study the benefits of adding a PPI to celecoxib and other coxibs.

Functional MRI, single-photon emission computed tomography, PET, and magnetic resonance spectroscopy have identified brain structures activated by pain. These include the primary and secondary somatosensory cortices, the insula, the anterior cingulate, the thalamus, the dorsal lateral prefrontal cortex, and the basal ganglia.

Similar studies have indicated fibromyalgia patients have abnormal activation in these regions, both at baseline and in response to painful stimuli.

Diffusion-weighted imaging (DWI) measures the restriction of water diffusion (the apparent diffusion coefficient or ADC) in the brain. Diffusion tensor imaging (DTI) measures the directional diffusion properties of water (fractional anisotropy or FA), and therefore, the integrity of organized tissue microstructures.

Dr. Pia C. Sundgren and Dr. Daniel J. Clauw, with colleagues at the University of Michigan in Ann Arbor, used DWI and DTI to look for cerebral abnormalities in fibromyalgia patients, versus healthy controls (Acad. Radiol. 2007;14:839–46).

The researchers studied 19 fibromyalgia patients (16 women), aged 20–57 years, and 25 pain-free controls (19 women). All subjects underwent MRI (1.5 T) including pre- and postcontrast enhanced axial and sagittal T1-weighted images, axial T-2 weighted images (with fat saturation), axial fluid attenuated inversion recovery (FLAIR) images, diffusion-weighted images, and postcontrast coronal T1-weighted images. The images were evaluated for brain volume loss, abnormal signal, abnormal contrast enhancement, abnormal diffusion, the presence of hemorrhage or mineralization, or other abnormalities.

First, the researchers developed whole-brain, gray matter-only, and white matter-only ADC histograms for each patient and control. Then histograms by group (fibromyalgia patients and controls) were calculated. ADC and FA maps also were calculated. Both ADC and FA are quantitative, with normal brain values of ADC around 0.7 × 10–3 mm

DTI maps were registered with postcontrast axial T1-weighted images. Standardized 50 mm

Clinical pain was assessed immediately before the DWI and DTI scans using a 10-cm visual analog scale. Pressure pain threshold was assessed before the DWI and DTI scans. Discrete pressure stimuli were applied to the subject's left thumbnail. Pain intensity ratings were recorded. Patients with fibromyalgia also were given the Center for Epidemiologic Studies Depression Scale questionnaire and the Spielberger's State-Trait Personality Inventory anxiety questionnaire. Specific cognitive beliefs about pain and control over pain were assessed using the Beliefs About Pain Control Questionnaire.

FA values were significantly less in the right thalamus for fibromyalgia patients, compared with controls. No differences were found in any other locations.

The differences in FA in the thalamus prompted the researchers to examine the relationship between the severity of fibromyalgia and FA within the group. Patients with more severe pain had lower FA values. Fibromyalgia patients tend to attribute their pain to an external event like minor trauma. The investigators found a negative correlation between the belief in an “external” cause of their pain and the FA values. This indicates these low right-thalamic values also were tied to a cognition known to be negatively associated with prognosis in chronic pain. Lower right-thalamic FA values also were tied to greater numbers of tender points, higher levels of depression, and a low pain threshold.

“The abnormalities that we've identified using this technique are actually less pronounced than what you'd find with [functional MRI] or PET or proton spectroscopy or other modalities. All of those modalities identify objective differences between fibromyalgia patients and controls with respect to pain processing regions,” said Dr. Clauw. “What you really find with all of those functional imaging techniques—this one included—they all give you different and somewhat complementary information. … There really is something wrong going on in the brains of these patients with fibromyalgia,” said Dr. Clauw.

The focal nature of these findings suggest these abnormalities are caused by ongoing demyelination or axonal injury but are rather due to neuronal dysfunction.

“If the tissue is less organized or the axons are dysfunctional, it might be seen as a reduction in the main directionality combined with alterations in the other diffusion directions resulting in a more round and less sphere/ellipsoid appearance of the diffusion directionality as can be seen in a more isotropic environment. This idea can be supported by the normal ADC value found here in the same region,” they wrote.

ADC and FA maps (top left and right) of a fibromyalgia patient: On the same FA map (bottom left), red white matter tracts indicate greater anisotropy. On another FA map (bottom right), there is less anisotropy in the dorsomedial aspect of right thalamus. IMAGES COURTESY DR. PIA C. SUNDGREN

Functional MRI, single-photon emission computed tomography, PET, and magnetic resonance spectroscopy have identified brain structures activated by pain. These include the primary and secondary somatosensory cortices, the insula, the anterior cingulate, the thalamus, the dorsal lateral prefrontal cortex, and the basal ganglia.

Similar studies have indicated fibromyalgia patients have abnormal activation in these regions, both at baseline and in response to painful stimuli.

Diffusion-weighted imaging (DWI) measures the restriction of water diffusion (the apparent diffusion coefficient or ADC) in the brain. Diffusion tensor imaging (DTI) measures the directional diffusion properties of water (fractional anisotropy or FA), and therefore, the integrity of organized tissue microstructures.

Dr. Pia C. Sundgren and Dr. Daniel J. Clauw, with colleagues at the University of Michigan in Ann Arbor, used DWI and DTI to look for cerebral abnormalities in fibromyalgia patients, versus healthy controls (Acad. Radiol. 2007;14:839–46).

The researchers studied 19 fibromyalgia patients (16 women), aged 20–57 years, and 25 pain-free controls (19 women). All subjects underwent MRI (1.5 T) including pre- and postcontrast enhanced axial and sagittal T1-weighted images, axial T-2 weighted images (with fat saturation), axial fluid attenuated inversion recovery (FLAIR) images, diffusion-weighted images, and postcontrast coronal T1-weighted images. The images were evaluated for brain volume loss, abnormal signal, abnormal contrast enhancement, abnormal diffusion, the presence of hemorrhage or mineralization, or other abnormalities.

First, the researchers developed whole-brain, gray matter-only, and white matter-only ADC histograms for each patient and control. Then histograms by group (fibromyalgia patients and controls) were calculated. ADC and FA maps also were calculated. Both ADC and FA are quantitative, with normal brain values of ADC around 0.7 × 10–3 mm

DTI maps were registered with postcontrast axial T1-weighted images. Standardized 50 mm

Clinical pain was assessed immediately before the DWI and DTI scans using a 10-cm visual analog scale. Pressure pain threshold was assessed before the DWI and DTI scans. Discrete pressure stimuli were applied to the subject's left thumbnail. Pain intensity ratings were recorded. Patients with fibromyalgia also were given the Center for Epidemiologic Studies Depression Scale questionnaire and the Spielberger's State-Trait Personality Inventory anxiety questionnaire. Specific cognitive beliefs about pain and control over pain were assessed using the Beliefs About Pain Control Questionnaire.

FA values were significantly less in the right thalamus for fibromyalgia patients, compared with controls. No differences were found in any other locations.

The differences in FA in the thalamus prompted the researchers to examine the relationship between the severity of fibromyalgia and FA within the group. Patients with more severe pain had lower FA values. Fibromyalgia patients tend to attribute their pain to an external event like minor trauma. The investigators found a negative correlation between the belief in an “external” cause of their pain and the FA values. This indicates these low right-thalamic values also were tied to a cognition known to be negatively associated with prognosis in chronic pain. Lower right-thalamic FA values also were tied to greater numbers of tender points, higher levels of depression, and a low pain threshold.

“The abnormalities that we've identified using this technique are actually less pronounced than what you'd find with [functional MRI] or PET or proton spectroscopy or other modalities. All of those modalities identify objective differences between fibromyalgia patients and controls with respect to pain processing regions,” said Dr. Clauw. “What you really find with all of those functional imaging techniques—this one included—they all give you different and somewhat complementary information. … There really is something wrong going on in the brains of these patients with fibromyalgia,” said Dr. Clauw.

The focal nature of these findings suggest these abnormalities are caused by ongoing demyelination or axonal injury but are rather due to neuronal dysfunction.

“If the tissue is less organized or the axons are dysfunctional, it might be seen as a reduction in the main directionality combined with alterations in the other diffusion directions resulting in a more round and less sphere/ellipsoid appearance of the diffusion directionality as can be seen in a more isotropic environment. This idea can be supported by the normal ADC value found here in the same region,” they wrote.

ADC and FA maps (top left and right) of a fibromyalgia patient: On the same FA map (bottom left), red white matter tracts indicate greater anisotropy. On another FA map (bottom right), there is less anisotropy in the dorsomedial aspect of right thalamus. IMAGES COURTESY DR. PIA C. SUNDGREN

Functional MRI, single-photon emission computed tomography, PET, and magnetic resonance spectroscopy have identified brain structures activated by pain. These include the primary and secondary somatosensory cortices, the insula, the anterior cingulate, the thalamus, the dorsal lateral prefrontal cortex, and the basal ganglia.

Similar studies have indicated fibromyalgia patients have abnormal activation in these regions, both at baseline and in response to painful stimuli.

Diffusion-weighted imaging (DWI) measures the restriction of water diffusion (the apparent diffusion coefficient or ADC) in the brain. Diffusion tensor imaging (DTI) measures the directional diffusion properties of water (fractional anisotropy or FA), and therefore, the integrity of organized tissue microstructures.

Dr. Pia C. Sundgren and Dr. Daniel J. Clauw, with colleagues at the University of Michigan in Ann Arbor, used DWI and DTI to look for cerebral abnormalities in fibromyalgia patients, versus healthy controls (Acad. Radiol. 2007;14:839–46).

The researchers studied 19 fibromyalgia patients (16 women), aged 20–57 years, and 25 pain-free controls (19 women). All subjects underwent MRI (1.5 T) including pre- and postcontrast enhanced axial and sagittal T1-weighted images, axial T-2 weighted images (with fat saturation), axial fluid attenuated inversion recovery (FLAIR) images, diffusion-weighted images, and postcontrast coronal T1-weighted images. The images were evaluated for brain volume loss, abnormal signal, abnormal contrast enhancement, abnormal diffusion, the presence of hemorrhage or mineralization, or other abnormalities.

First, the researchers developed whole-brain, gray matter-only, and white matter-only ADC histograms for each patient and control. Then histograms by group (fibromyalgia patients and controls) were calculated. ADC and FA maps also were calculated. Both ADC and FA are quantitative, with normal brain values of ADC around 0.7 × 10–3 mm

DTI maps were registered with postcontrast axial T1-weighted images. Standardized 50 mm

Clinical pain was assessed immediately before the DWI and DTI scans using a 10-cm visual analog scale. Pressure pain threshold was assessed before the DWI and DTI scans. Discrete pressure stimuli were applied to the subject's left thumbnail. Pain intensity ratings were recorded. Patients with fibromyalgia also were given the Center for Epidemiologic Studies Depression Scale questionnaire and the Spielberger's State-Trait Personality Inventory anxiety questionnaire. Specific cognitive beliefs about pain and control over pain were assessed using the Beliefs About Pain Control Questionnaire.

FA values were significantly less in the right thalamus for fibromyalgia patients, compared with controls. No differences were found in any other locations.

The differences in FA in the thalamus prompted the researchers to examine the relationship between the severity of fibromyalgia and FA within the group. Patients with more severe pain had lower FA values. Fibromyalgia patients tend to attribute their pain to an external event like minor trauma. The investigators found a negative correlation between the belief in an “external” cause of their pain and the FA values. This indicates these low right-thalamic values also were tied to a cognition known to be negatively associated with prognosis in chronic pain. Lower right-thalamic FA values also were tied to greater numbers of tender points, higher levels of depression, and a low pain threshold.

“The abnormalities that we've identified using this technique are actually less pronounced than what you'd find with [functional MRI] or PET or proton spectroscopy or other modalities. All of those modalities identify objective differences between fibromyalgia patients and controls with respect to pain processing regions,” said Dr. Clauw. “What you really find with all of those functional imaging techniques—this one included—they all give you different and somewhat complementary information. … There really is something wrong going on in the brains of these patients with fibromyalgia,” said Dr. Clauw.

The focal nature of these findings suggest these abnormalities are caused by ongoing demyelination or axonal injury but are rather due to neuronal dysfunction.

“If the tissue is less organized or the axons are dysfunctional, it might be seen as a reduction in the main directionality combined with alterations in the other diffusion directions resulting in a more round and less sphere/ellipsoid appearance of the diffusion directionality as can be seen in a more isotropic environment. This idea can be supported by the normal ADC value found here in the same region,” they wrote.

ADC and FA maps (top left and right) of a fibromyalgia patient: On the same FA map (bottom left), red white matter tracts indicate greater anisotropy. On another FA map (bottom right), there is less anisotropy in the dorsomedial aspect of right thalamus. IMAGES COURTESY DR. PIA C. SUNDGREN

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