Rheumatoid Arthritis

COPENHAGEN — The addition of tocilizumab to methotrexate therapy is a promising new option for rheumatoid arthritis patients who do not fully respond to treatment with the disease-modifying antirheumatic drug alone, Dr. Joel M. Kremer said at the annual European Congress on Rheumatology.

Dr. Kremer, director of research at the Center for Rheumatology LLC in Albany, N.Y., presented 1-year data from the international LITHE (Tocilizumab Safety and the Prevention of Structural Joint Damage) study showing that the anti-interleukin-6 monoclonal antibody inhibits structural joint damage and improves physical function and clinical disease activity, compared with methotrexate alone.

The randomized, double-blind, placebo-controlled LITHE study, which was sponsored by Roche, enrolled 1,196 patients with moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate. Patients were randomized to receive a 4-mg/kg or 8-mg/kg infusion of tocilizumab (Actemra) every 4 weeks in combination with stable doses of methotrexate or methotrexate/placebo. The study's primary end points included ACR 20 response at 24 weeks and change from baseline in Genant-modified Total Sharp Score (GmTSS) and physical function at 52 weeks, measured by area under the curve (AUC) of change from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI), Dr. Kremer explained.

At 24 weeks, ACR 20 response was achieved by 56% and 51%, respectively, in the tocilizumab 8-mg and 4-mg combination therapy groups, compared with 27% of the methotrexate-only group, Dr. Kremer said, noting that significantly more patients in both combination therapy groups achieved ARC 20/50/70 responses at week 52.

Also at 52 weeks, there were significantly more patients in the combination therapy groups without radiographic progression from baseline, compared with the methotrexate-only group. Total GmTSS change from baseline for the tocilizumab (8 mg)/methotrexate, the tocilizumab (4 mg)/methotrexate, and the methotrexate-only groups were 0.29, 0.34 and 1.13, respectively. The respective percentages of patients achieving no progression in GmTSS were 85%, 81%, and 67%, Dr. Kremer said. The HAQ-DI AUC changes from baseline adjusted mean scores were −144.1, −128.4 and −58.1, respectively. At 24 and 52 weeks, the DAS28 (Disease Activity Score based on 28 joints) clinical remission scores were significantly greater in the combination therapy groups, compared with the methotrexate-only group. In both combination therapy groups, the DAS28 remission rate increased from week 24 to week 52, indicating an increasing magnitude of clinical benefit over time, he said.

“Tocilizumab represents a new approach to treating severe arthritis, but as always, the decision to use a particular biologic agent is not cast in stone” Dr. Kremer said in an interview. “There will always be patients in any busy practice who have tried and failed the multiple agents previously available.” In these patients, he said, “trying a new mechanism of action, while watching carefully for the emergence of side effects, is reasonable.”

In particular, patients must be monitored for abnormalities in transaminase enzymes, which would require an adjustment in the dose of either medication, Dr. Kremer said. In the event of significant increases in lipid levels in a patient with underlying risk factors for cardiovascular disease, strong consideration should be given to the initiation of a statin agent, he said.

Dr. Kremer, who is also the founder and president of CORRONA (Consortium of Rheumatology Researchers of North America), disclosed that he has received grants for clinical research from—and has served as a consultant for—Abbott Laboratories, Amgen Inc., Bristol-Myers Squibb Co., Centocor Inc., Genentech Inc., and Roche.

COPENHAGEN — The addition of tocilizumab to methotrexate therapy is a promising new option for rheumatoid arthritis patients who do not fully respond to treatment with the disease-modifying antirheumatic drug alone, Dr. Joel M. Kremer said at the annual European Congress on Rheumatology.

Dr. Kremer, director of research at the Center for Rheumatology LLC in Albany, N.Y., presented 1-year data from the international LITHE (Tocilizumab Safety and the Prevention of Structural Joint Damage) study showing that the anti-interleukin-6 monoclonal antibody inhibits structural joint damage and improves physical function and clinical disease activity, compared with methotrexate alone.

The randomized, double-blind, placebo-controlled LITHE study, which was sponsored by Roche, enrolled 1,196 patients with moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate. Patients were randomized to receive a 4-mg/kg or 8-mg/kg infusion of tocilizumab (Actemra) every 4 weeks in combination with stable doses of methotrexate or methotrexate/placebo. The study's primary end points included ACR 20 response at 24 weeks and change from baseline in Genant-modified Total Sharp Score (GmTSS) and physical function at 52 weeks, measured by area under the curve (AUC) of change from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI), Dr. Kremer explained.

At 24 weeks, ACR 20 response was achieved by 56% and 51%, respectively, in the tocilizumab 8-mg and 4-mg combination therapy groups, compared with 27% of the methotrexate-only group, Dr. Kremer said, noting that significantly more patients in both combination therapy groups achieved ARC 20/50/70 responses at week 52.

Also at 52 weeks, there were significantly more patients in the combination therapy groups without radiographic progression from baseline, compared with the methotrexate-only group. Total GmTSS change from baseline for the tocilizumab (8 mg)/methotrexate, the tocilizumab (4 mg)/methotrexate, and the methotrexate-only groups were 0.29, 0.34 and 1.13, respectively. The respective percentages of patients achieving no progression in GmTSS were 85%, 81%, and 67%, Dr. Kremer said. The HAQ-DI AUC changes from baseline adjusted mean scores were −144.1, −128.4 and −58.1, respectively. At 24 and 52 weeks, the DAS28 (Disease Activity Score based on 28 joints) clinical remission scores were significantly greater in the combination therapy groups, compared with the methotrexate-only group. In both combination therapy groups, the DAS28 remission rate increased from week 24 to week 52, indicating an increasing magnitude of clinical benefit over time, he said.

“Tocilizumab represents a new approach to treating severe arthritis, but as always, the decision to use a particular biologic agent is not cast in stone” Dr. Kremer said in an interview. “There will always be patients in any busy practice who have tried and failed the multiple agents previously available.” In these patients, he said, “trying a new mechanism of action, while watching carefully for the emergence of side effects, is reasonable.”

In particular, patients must be monitored for abnormalities in transaminase enzymes, which would require an adjustment in the dose of either medication, Dr. Kremer said. In the event of significant increases in lipid levels in a patient with underlying risk factors for cardiovascular disease, strong consideration should be given to the initiation of a statin agent, he said.

Dr. Kremer, who is also the founder and president of CORRONA (Consortium of Rheumatology Researchers of North America), disclosed that he has received grants for clinical research from—and has served as a consultant for—Abbott Laboratories, Amgen Inc., Bristol-Myers Squibb Co., Centocor Inc., Genentech Inc., and Roche.

COPENHAGEN — The addition of tocilizumab to methotrexate therapy is a promising new option for rheumatoid arthritis patients who do not fully respond to treatment with the disease-modifying antirheumatic drug alone, Dr. Joel M. Kremer said at the annual European Congress on Rheumatology.

Dr. Kremer, director of research at the Center for Rheumatology LLC in Albany, N.Y., presented 1-year data from the international LITHE (Tocilizumab Safety and the Prevention of Structural Joint Damage) study showing that the anti-interleukin-6 monoclonal antibody inhibits structural joint damage and improves physical function and clinical disease activity, compared with methotrexate alone.

The randomized, double-blind, placebo-controlled LITHE study, which was sponsored by Roche, enrolled 1,196 patients with moderate to severe rheumatoid arthritis who had an inadequate response to methotrexate. Patients were randomized to receive a 4-mg/kg or 8-mg/kg infusion of tocilizumab (Actemra) every 4 weeks in combination with stable doses of methotrexate or methotrexate/placebo. The study's primary end points included ACR 20 response at 24 weeks and change from baseline in Genant-modified Total Sharp Score (GmTSS) and physical function at 52 weeks, measured by area under the curve (AUC) of change from baseline in the Health Assessment Questionnaire Disability Index (HAQ-DI), Dr. Kremer explained.

At 24 weeks, ACR 20 response was achieved by 56% and 51%, respectively, in the tocilizumab 8-mg and 4-mg combination therapy groups, compared with 27% of the methotrexate-only group, Dr. Kremer said, noting that significantly more patients in both combination therapy groups achieved ARC 20/50/70 responses at week 52.

Also at 52 weeks, there were significantly more patients in the combination therapy groups without radiographic progression from baseline, compared with the methotrexate-only group. Total GmTSS change from baseline for the tocilizumab (8 mg)/methotrexate, the tocilizumab (4 mg)/methotrexate, and the methotrexate-only groups were 0.29, 0.34 and 1.13, respectively. The respective percentages of patients achieving no progression in GmTSS were 85%, 81%, and 67%, Dr. Kremer said. The HAQ-DI AUC changes from baseline adjusted mean scores were −144.1, −128.4 and −58.1, respectively. At 24 and 52 weeks, the DAS28 (Disease Activity Score based on 28 joints) clinical remission scores were significantly greater in the combination therapy groups, compared with the methotrexate-only group. In both combination therapy groups, the DAS28 remission rate increased from week 24 to week 52, indicating an increasing magnitude of clinical benefit over time, he said.

“Tocilizumab represents a new approach to treating severe arthritis, but as always, the decision to use a particular biologic agent is not cast in stone” Dr. Kremer said in an interview. “There will always be patients in any busy practice who have tried and failed the multiple agents previously available.” In these patients, he said, “trying a new mechanism of action, while watching carefully for the emergence of side effects, is reasonable.”

In particular, patients must be monitored for abnormalities in transaminase enzymes, which would require an adjustment in the dose of either medication, Dr. Kremer said. In the event of significant increases in lipid levels in a patient with underlying risk factors for cardiovascular disease, strong consideration should be given to the initiation of a statin agent, he said.

Dr. Kremer, who is also the founder and president of CORRONA (Consortium of Rheumatology Researchers of North America), disclosed that he has received grants for clinical research from—and has served as a consultant for—Abbott Laboratories, Amgen Inc., Bristol-Myers Squibb Co., Centocor Inc., Genentech Inc., and Roche.

COPENHAGEN — Treatment with etanercept produced significant clinical improvement in heel enthesitis associated with spondyloarthritis, according to Dr. Maxime Dougados.

“This study demonstrates the efficacy of etanercept in [enthesopathy] related to spondyloarthritis, whatever the underlying disease” including ankylosing spondylitis or psoriatic arthritis, said Prof. Dougados, director of the research center in the department of rheumatology at Hôpital Cochin, Paris.

This 12-week, controlled study with 24 patients is the first prospective, placebo-controlled trial of a treatment for enthesopathy related to spondyloarthritis, added Prof. Dougados, who presented the findings at the annual European Congress of Rheumatology.

The benefit on symptoms from 12 weeks of etanercept treatment vs. placebo was clinically as well as statistically significant.

Patients on etanercept experienced substantial improvements from baseline on a variety of measures, including their global assessment (the primary outcome), heel pain, and WOMAC (Western Ontario and McMaster Universities) osteoarthritis index functional subscale score.

“Despite the small sample size [a total of 24 patients], the results seen not only in the primary variable but also in all the secondary variables are strongly in favor” of etanercept's efficacy for heel enthesitis, Prof. Dougados said in an interview with RHEUMATOLOGY NEWS. “I hope the trial will be replicated by evaluating the other TNF [tumor necrosis factor] blockers.”

Heel enthesitis is common in patients with spondyloarthritis regardless of the underlying cause, occurring in 40%–50% of these patients, and can be disabling, according to Dr. Dougados.

Although etanercept and other TNF-blocking drugs have proved to be effective for reducing many of the main clinical manifestations of spondyloarthritis (such as peripheral arthritis, axial symptoms, and psoriatic skin lesions), the impact of these treatments on heel enthesitis was not known prior to this investigation.

The study, which was done at six hospitals in France, Germany, and the Netherlands, enrolled patients older than 18 years who had spondyloarthritis and related heel enthesitis that was refractory to standard treatment with NSAIDs and local injections of corticosteroids.

The AS patients' heel enthesitis was documented by their inferior and/or posterior heel pain and by an MRI scan showing bone marrow edema in the calcaneus adjacent to the insertion of either the Achilles tendon or plantar fascia. The average age of enrolled patients was 37 years.

In all, 12 patients began a 12-week course of standard etanercept treatment, and the other 12 received placebo.

During the study, five patients stopped treatment (four in the placebo group because of lack of efficacy, and one in the etanercept group because of a severe infection in the form of foot cellulitis that required hospitalization).

At the end of the treatment period, the average change in patients' global score on a visual analog scale of 0-100 was a reduction of 29 points from a baseline average of 70 in the etanercept-treated patients, compared with a reduction of 11 points in the placebo-treated patients.

After 2 weeks, the patients receiving etanercept began to show improvement in global score and other measurements.

By the end of 8 weeks, those differences between active treatment and placebo reached a statistically significant difference, compared with placebo, reported Prof. Dougados, who is also professor of rheumatology at René Descartes University in Paris.

During the study, five patients on etanercept and three on placebo had infections, primarily upper respiratory. All resolved once treatment was complete.

The well-documented risk for infection from treatment with etanercept or other TNF blockers must be balanced against the risk from conventional treatments for enthesopathy, as well as the risk that enthesitis poses for causing disability in young patients, Dr. Dougados noted.

The study was sponsored by Wyeth Pharmaceuticals, the company that markets the drug etanercept.

Prof. Dougados has been a consultant to Wyeth and to several other drug companies.

The infection risk seen with all anti-TNF agents is outweighed by the benefit of preventing disability. DR. DOUGADOS

On STIR MR images (above), note the areas of high signal in the inferior calcaneus that correspond to bone marrow edema.

Sagittal T1 MR images of the same heels show thickening with heterogeneous high signal of the plantar fascia in a patient with heel pain due to AS-related enthesitis. Images courtesy Prof. Maxime Dougados

COPENHAGEN — Treatment with etanercept produced significant clinical improvement in heel enthesitis associated with spondyloarthritis, according to Dr. Maxime Dougados.

“This study demonstrates the efficacy of etanercept in [enthesopathy] related to spondyloarthritis, whatever the underlying disease” including ankylosing spondylitis or psoriatic arthritis, said Prof. Dougados, director of the research center in the department of rheumatology at Hôpital Cochin, Paris.

This 12-week, controlled study with 24 patients is the first prospective, placebo-controlled trial of a treatment for enthesopathy related to spondyloarthritis, added Prof. Dougados, who presented the findings at the annual European Congress of Rheumatology.

The benefit on symptoms from 12 weeks of etanercept treatment vs. placebo was clinically as well as statistically significant.

Patients on etanercept experienced substantial improvements from baseline on a variety of measures, including their global assessment (the primary outcome), heel pain, and WOMAC (Western Ontario and McMaster Universities) osteoarthritis index functional subscale score.

“Despite the small sample size [a total of 24 patients], the results seen not only in the primary variable but also in all the secondary variables are strongly in favor” of etanercept's efficacy for heel enthesitis, Prof. Dougados said in an interview with RHEUMATOLOGY NEWS. “I hope the trial will be replicated by evaluating the other TNF [tumor necrosis factor] blockers.”

Heel enthesitis is common in patients with spondyloarthritis regardless of the underlying cause, occurring in 40%–50% of these patients, and can be disabling, according to Dr. Dougados.

Although etanercept and other TNF-blocking drugs have proved to be effective for reducing many of the main clinical manifestations of spondyloarthritis (such as peripheral arthritis, axial symptoms, and psoriatic skin lesions), the impact of these treatments on heel enthesitis was not known prior to this investigation.

The study, which was done at six hospitals in France, Germany, and the Netherlands, enrolled patients older than 18 years who had spondyloarthritis and related heel enthesitis that was refractory to standard treatment with NSAIDs and local injections of corticosteroids.

The AS patients' heel enthesitis was documented by their inferior and/or posterior heel pain and by an MRI scan showing bone marrow edema in the calcaneus adjacent to the insertion of either the Achilles tendon or plantar fascia. The average age of enrolled patients was 37 years.

In all, 12 patients began a 12-week course of standard etanercept treatment, and the other 12 received placebo.

During the study, five patients stopped treatment (four in the placebo group because of lack of efficacy, and one in the etanercept group because of a severe infection in the form of foot cellulitis that required hospitalization).

At the end of the treatment period, the average change in patients' global score on a visual analog scale of 0-100 was a reduction of 29 points from a baseline average of 70 in the etanercept-treated patients, compared with a reduction of 11 points in the placebo-treated patients.

After 2 weeks, the patients receiving etanercept began to show improvement in global score and other measurements.

By the end of 8 weeks, those differences between active treatment and placebo reached a statistically significant difference, compared with placebo, reported Prof. Dougados, who is also professor of rheumatology at René Descartes University in Paris.

During the study, five patients on etanercept and three on placebo had infections, primarily upper respiratory. All resolved once treatment was complete.

The well-documented risk for infection from treatment with etanercept or other TNF blockers must be balanced against the risk from conventional treatments for enthesopathy, as well as the risk that enthesitis poses for causing disability in young patients, Dr. Dougados noted.

The study was sponsored by Wyeth Pharmaceuticals, the company that markets the drug etanercept.

Prof. Dougados has been a consultant to Wyeth and to several other drug companies.

The infection risk seen with all anti-TNF agents is outweighed by the benefit of preventing disability. DR. DOUGADOS

On STIR MR images (above), note the areas of high signal in the inferior calcaneus that correspond to bone marrow edema.

Sagittal T1 MR images of the same heels show thickening with heterogeneous high signal of the plantar fascia in a patient with heel pain due to AS-related enthesitis. Images courtesy Prof. Maxime Dougados

COPENHAGEN — Treatment with etanercept produced significant clinical improvement in heel enthesitis associated with spondyloarthritis, according to Dr. Maxime Dougados.

“This study demonstrates the efficacy of etanercept in [enthesopathy] related to spondyloarthritis, whatever the underlying disease” including ankylosing spondylitis or psoriatic arthritis, said Prof. Dougados, director of the research center in the department of rheumatology at Hôpital Cochin, Paris.

This 12-week, controlled study with 24 patients is the first prospective, placebo-controlled trial of a treatment for enthesopathy related to spondyloarthritis, added Prof. Dougados, who presented the findings at the annual European Congress of Rheumatology.

The benefit on symptoms from 12 weeks of etanercept treatment vs. placebo was clinically as well as statistically significant.

Patients on etanercept experienced substantial improvements from baseline on a variety of measures, including their global assessment (the primary outcome), heel pain, and WOMAC (Western Ontario and McMaster Universities) osteoarthritis index functional subscale score.

“Despite the small sample size [a total of 24 patients], the results seen not only in the primary variable but also in all the secondary variables are strongly in favor” of etanercept's efficacy for heel enthesitis, Prof. Dougados said in an interview with RHEUMATOLOGY NEWS. “I hope the trial will be replicated by evaluating the other TNF [tumor necrosis factor] blockers.”

Heel enthesitis is common in patients with spondyloarthritis regardless of the underlying cause, occurring in 40%–50% of these patients, and can be disabling, according to Dr. Dougados.

Although etanercept and other TNF-blocking drugs have proved to be effective for reducing many of the main clinical manifestations of spondyloarthritis (such as peripheral arthritis, axial symptoms, and psoriatic skin lesions), the impact of these treatments on heel enthesitis was not known prior to this investigation.

The study, which was done at six hospitals in France, Germany, and the Netherlands, enrolled patients older than 18 years who had spondyloarthritis and related heel enthesitis that was refractory to standard treatment with NSAIDs and local injections of corticosteroids.

The AS patients' heel enthesitis was documented by their inferior and/or posterior heel pain and by an MRI scan showing bone marrow edema in the calcaneus adjacent to the insertion of either the Achilles tendon or plantar fascia. The average age of enrolled patients was 37 years.

In all, 12 patients began a 12-week course of standard etanercept treatment, and the other 12 received placebo.

During the study, five patients stopped treatment (four in the placebo group because of lack of efficacy, and one in the etanercept group because of a severe infection in the form of foot cellulitis that required hospitalization).

At the end of the treatment period, the average change in patients' global score on a visual analog scale of 0-100 was a reduction of 29 points from a baseline average of 70 in the etanercept-treated patients, compared with a reduction of 11 points in the placebo-treated patients.

After 2 weeks, the patients receiving etanercept began to show improvement in global score and other measurements.

By the end of 8 weeks, those differences between active treatment and placebo reached a statistically significant difference, compared with placebo, reported Prof. Dougados, who is also professor of rheumatology at René Descartes University in Paris.

During the study, five patients on etanercept and three on placebo had infections, primarily upper respiratory. All resolved once treatment was complete.

The well-documented risk for infection from treatment with etanercept or other TNF blockers must be balanced against the risk from conventional treatments for enthesopathy, as well as the risk that enthesitis poses for causing disability in young patients, Dr. Dougados noted.

The study was sponsored by Wyeth Pharmaceuticals, the company that markets the drug etanercept.

Prof. Dougados has been a consultant to Wyeth and to several other drug companies.

The infection risk seen with all anti-TNF agents is outweighed by the benefit of preventing disability. DR. DOUGADOS

On STIR MR images (above), note the areas of high signal in the inferior calcaneus that correspond to bone marrow edema.

Sagittal T1 MR images of the same heels show thickening with heterogeneous high signal of the plantar fascia in a patient with heel pain due to AS-related enthesitis. Images courtesy Prof. Maxime Dougados

CHICAGO — An updated guideline addressing persistent pain in older people takes a tough stance on the use of nonsteroidal anti-inflammatory drugs.

The American Geriatrics Society (AGS) guideline recommends that acetaminophen be considered for initial and ongoing treatment of persistent pain, particularly musculoskeletal pain. But in a significant departure from its 2002 guideline, the AGS recommends that nonselective NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors “be considered rarely, and with extreme caution, in highly selected individuals.”

The AGS had recommended that seniors use over-the-counter or prescription NSAIDs (such as aspirin or ibuprofen) or COX-2 inhibitors before being prescribed an opioid. The current recommendation reflects recent good evidence that this is a risky strategy in older people, panel member Dr. James Katz said at the society's annual meeting, where the guidelines (“Pharmacological Management of Persistent Pain in Older Persons”) were released.

Conventional NSAIDs are associated with adverse gastrointestinal events in 20% of patients, with 107,000 hospitalizations and 16,500 deaths attributed yearly to NSAID-related GI complications.

COX-2 inhibitors seem to produce fewer upper GI events than do other NSAIDs, but “all nonsteroidals, whether they are [COX-2 inhibitors] or not, have a significant portfolio of adverse effects that is noteworthy for the elderly population,” said Dr. Katz, director of rheumatology at George Washington University in Washington. “They can aggravate hypertension, they can cause renal impairment by a variety of mechanisms, [they can cause] edema [and] gastrointestinal problems, and now we know cardiovascular and cerebrovascular disease can be attributed to nonsteroidal interaction.”

Last year's study of 336,906 community-dwelling Medicaid beneficiaries by the VA Tennessee Valley Healthcare System extended concerns about COX-2 selective inhibitors to cerebrovascular disease, said Dr. Katz. The study suggested an increased risk of stroke with rofecoxib (Vioxx) and valdecoxib (Bextra), compared with the effects of nonselective agents (Stroke 2008;39:2037-45). The finding was not statistically significant, he noted, but both drugs have been withdrawn from the market.

Recent evidence also showed that combining a conventional NSAID with low-dose aspirin therapy increases the risk of GI bleeding beyond that of the NSAID alone (Curr. Opin. Rheumatol. 2008;20:239-45). In 2006, the Food and Drug Administration warned against taking aspirin and ibuprofen together because ibuprofen interferes with aspirin's acetylation effect.

More research is needed to determine whether other NSAIDs interfere with the cardioprotective benefits of low-dose aspirin, said Dr. Katz, who was part of a panel unveiling the guidelines at the meeting. Panel members also said that more data are needed on the safety of topical preparations of NSAIDs.

The revised guideline recommends the eradication of Helicobacter pylori prior to initiating NSAIDs for pain, and the use of a proton pump inhibitor or misoprostol for gastrointestinal protection in older persons taking nonselective NSAIDs or in patients taking a COX-2 selective inhibitor with aspirin.

The guideline recommends that physicians consider opioid therapy for patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. People with continual or frequent daily pain may be treated with around-the-clock, time-contingent dosing aimed at achieving steady-state opioid therapy, said Dr. Perry Fine of the pain management center at the University of Utah, Salt Lake City.

He noted the guideline's caution concerning methadone, and recommended that only clinicians who are well versed in its use and risks initiate and titrate the drug. “That doesn't mean you don't do it,” said Dr. Fine, “but hook yourself up to someone who has a lot of experience in this when you believe this drug is indicated, if you don't already have the experience.”

Methadone-related deaths during pain treatment have risen up to eightfold in the past few years. This is largely because methadone is attractive as a relatively inexpensive drug, but it has an unpredictable and long half-life. That the drug stays active is a blessing, but that quality is also a problem because it accumulates in the body, Dr. Fine said.

Earlier this year, the American Pain Society and the American Academy of Pain Medicine released clinical guidance on the management of opioid therapy for chronic noncancer pain (J. Pain 2009;10:113-30). Like the AGS guidelines, that document stressed the need for clinicians to regularly assess patients for pain intensity, functional status, side effects, and safe and responsible use.

The updated AGS guideline gives new references and discussions on the use and limitations of newer adjuvant, topical, and other drugs for recalcitrant pain.

“Persistent pain isn't a normal part of aging and should not be ignored,” Dr. Cheryl Phillips, AGS president, said in a statement. “As seniors become susceptible to more complex health ailments, the need for a clear and precise pain management plan is key.”

The AGS published its first pain guideline in 1998. To arrive at the 2009 recommendations, a panel of experts conducted a systematic review of 2,400 abstracts and 240 data-based, full-text articles. The panel focused on pharmacotherapy because it is the most common strategy used for pain management among elderly people, as well as the area of greatest risk, said Dr. Bruce Ferrell of the University of California, Los Angeles, who chaired the panel. The 2009 update is to be published in an upcoming issue of the Journal of the American Geriatrics Society.

Dr. Katz disclosed that he has served as a paid consultant in the last 12 months for the American Academy of CME Inc. and for UCB Pharma Inc. Dr. Fine said he is a paid consultant or speaker for numerous pharmaceutical companies and has commercial interests in Johnson & Johnson and Cephalon Inc. Dr. Ferrell disclosed no relevant conflict of interest.

Members of the American Geriatric Society panel on the pharmacologic management of persistent pain in older persons include (from left to right) Dr. Bruce Ferrell, Dr. Perry Fine, Dr. James Katz, Dr. F. Michael Gloth III, and Lori Reisner, Pharm.D., shown discussing the release of the guidelines at the AGS annual meeting. Patrice Wendling/Elsevier Global Medical News

CHICAGO — An updated guideline addressing persistent pain in older people takes a tough stance on the use of nonsteroidal anti-inflammatory drugs.

The American Geriatrics Society (AGS) guideline recommends that acetaminophen be considered for initial and ongoing treatment of persistent pain, particularly musculoskeletal pain. But in a significant departure from its 2002 guideline, the AGS recommends that nonselective NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors “be considered rarely, and with extreme caution, in highly selected individuals.”

The AGS had recommended that seniors use over-the-counter or prescription NSAIDs (such as aspirin or ibuprofen) or COX-2 inhibitors before being prescribed an opioid. The current recommendation reflects recent good evidence that this is a risky strategy in older people, panel member Dr. James Katz said at the society's annual meeting, where the guidelines (“Pharmacological Management of Persistent Pain in Older Persons”) were released.

Conventional NSAIDs are associated with adverse gastrointestinal events in 20% of patients, with 107,000 hospitalizations and 16,500 deaths attributed yearly to NSAID-related GI complications.

COX-2 inhibitors seem to produce fewer upper GI events than do other NSAIDs, but “all nonsteroidals, whether they are [COX-2 inhibitors] or not, have a significant portfolio of adverse effects that is noteworthy for the elderly population,” said Dr. Katz, director of rheumatology at George Washington University in Washington. “They can aggravate hypertension, they can cause renal impairment by a variety of mechanisms, [they can cause] edema [and] gastrointestinal problems, and now we know cardiovascular and cerebrovascular disease can be attributed to nonsteroidal interaction.”

Last year's study of 336,906 community-dwelling Medicaid beneficiaries by the VA Tennessee Valley Healthcare System extended concerns about COX-2 selective inhibitors to cerebrovascular disease, said Dr. Katz. The study suggested an increased risk of stroke with rofecoxib (Vioxx) and valdecoxib (Bextra), compared with the effects of nonselective agents (Stroke 2008;39:2037-45). The finding was not statistically significant, he noted, but both drugs have been withdrawn from the market.

Recent evidence also showed that combining a conventional NSAID with low-dose aspirin therapy increases the risk of GI bleeding beyond that of the NSAID alone (Curr. Opin. Rheumatol. 2008;20:239-45). In 2006, the Food and Drug Administration warned against taking aspirin and ibuprofen together because ibuprofen interferes with aspirin's acetylation effect.

More research is needed to determine whether other NSAIDs interfere with the cardioprotective benefits of low-dose aspirin, said Dr. Katz, who was part of a panel unveiling the guidelines at the meeting. Panel members also said that more data are needed on the safety of topical preparations of NSAIDs.

The revised guideline recommends the eradication of Helicobacter pylori prior to initiating NSAIDs for pain, and the use of a proton pump inhibitor or misoprostol for gastrointestinal protection in older persons taking nonselective NSAIDs or in patients taking a COX-2 selective inhibitor with aspirin.

The guideline recommends that physicians consider opioid therapy for patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. People with continual or frequent daily pain may be treated with around-the-clock, time-contingent dosing aimed at achieving steady-state opioid therapy, said Dr. Perry Fine of the pain management center at the University of Utah, Salt Lake City.

He noted the guideline's caution concerning methadone, and recommended that only clinicians who are well versed in its use and risks initiate and titrate the drug. “That doesn't mean you don't do it,” said Dr. Fine, “but hook yourself up to someone who has a lot of experience in this when you believe this drug is indicated, if you don't already have the experience.”

Methadone-related deaths during pain treatment have risen up to eightfold in the past few years. This is largely because methadone is attractive as a relatively inexpensive drug, but it has an unpredictable and long half-life. That the drug stays active is a blessing, but that quality is also a problem because it accumulates in the body, Dr. Fine said.

Earlier this year, the American Pain Society and the American Academy of Pain Medicine released clinical guidance on the management of opioid therapy for chronic noncancer pain (J. Pain 2009;10:113-30). Like the AGS guidelines, that document stressed the need for clinicians to regularly assess patients for pain intensity, functional status, side effects, and safe and responsible use.

The updated AGS guideline gives new references and discussions on the use and limitations of newer adjuvant, topical, and other drugs for recalcitrant pain.

“Persistent pain isn't a normal part of aging and should not be ignored,” Dr. Cheryl Phillips, AGS president, said in a statement. “As seniors become susceptible to more complex health ailments, the need for a clear and precise pain management plan is key.”

The AGS published its first pain guideline in 1998. To arrive at the 2009 recommendations, a panel of experts conducted a systematic review of 2,400 abstracts and 240 data-based, full-text articles. The panel focused on pharmacotherapy because it is the most common strategy used for pain management among elderly people, as well as the area of greatest risk, said Dr. Bruce Ferrell of the University of California, Los Angeles, who chaired the panel. The 2009 update is to be published in an upcoming issue of the Journal of the American Geriatrics Society.

Dr. Katz disclosed that he has served as a paid consultant in the last 12 months for the American Academy of CME Inc. and for UCB Pharma Inc. Dr. Fine said he is a paid consultant or speaker for numerous pharmaceutical companies and has commercial interests in Johnson & Johnson and Cephalon Inc. Dr. Ferrell disclosed no relevant conflict of interest.

Members of the American Geriatric Society panel on the pharmacologic management of persistent pain in older persons include (from left to right) Dr. Bruce Ferrell, Dr. Perry Fine, Dr. James Katz, Dr. F. Michael Gloth III, and Lori Reisner, Pharm.D., shown discussing the release of the guidelines at the AGS annual meeting. Patrice Wendling/Elsevier Global Medical News

CHICAGO — An updated guideline addressing persistent pain in older people takes a tough stance on the use of nonsteroidal anti-inflammatory drugs.

The American Geriatrics Society (AGS) guideline recommends that acetaminophen be considered for initial and ongoing treatment of persistent pain, particularly musculoskeletal pain. But in a significant departure from its 2002 guideline, the AGS recommends that nonselective NSAIDs and cyclooxygenase-2 (COX-2) selective inhibitors “be considered rarely, and with extreme caution, in highly selected individuals.”

The AGS had recommended that seniors use over-the-counter or prescription NSAIDs (such as aspirin or ibuprofen) or COX-2 inhibitors before being prescribed an opioid. The current recommendation reflects recent good evidence that this is a risky strategy in older people, panel member Dr. James Katz said at the society's annual meeting, where the guidelines (“Pharmacological Management of Persistent Pain in Older Persons”) were released.

Conventional NSAIDs are associated with adverse gastrointestinal events in 20% of patients, with 107,000 hospitalizations and 16,500 deaths attributed yearly to NSAID-related GI complications.

COX-2 inhibitors seem to produce fewer upper GI events than do other NSAIDs, but “all nonsteroidals, whether they are [COX-2 inhibitors] or not, have a significant portfolio of adverse effects that is noteworthy for the elderly population,” said Dr. Katz, director of rheumatology at George Washington University in Washington. “They can aggravate hypertension, they can cause renal impairment by a variety of mechanisms, [they can cause] edema [and] gastrointestinal problems, and now we know cardiovascular and cerebrovascular disease can be attributed to nonsteroidal interaction.”

Last year's study of 336,906 community-dwelling Medicaid beneficiaries by the VA Tennessee Valley Healthcare System extended concerns about COX-2 selective inhibitors to cerebrovascular disease, said Dr. Katz. The study suggested an increased risk of stroke with rofecoxib (Vioxx) and valdecoxib (Bextra), compared with the effects of nonselective agents (Stroke 2008;39:2037-45). The finding was not statistically significant, he noted, but both drugs have been withdrawn from the market.

Recent evidence also showed that combining a conventional NSAID with low-dose aspirin therapy increases the risk of GI bleeding beyond that of the NSAID alone (Curr. Opin. Rheumatol. 2008;20:239-45). In 2006, the Food and Drug Administration warned against taking aspirin and ibuprofen together because ibuprofen interferes with aspirin's acetylation effect.

More research is needed to determine whether other NSAIDs interfere with the cardioprotective benefits of low-dose aspirin, said Dr. Katz, who was part of a panel unveiling the guidelines at the meeting. Panel members also said that more data are needed on the safety of topical preparations of NSAIDs.

The revised guideline recommends the eradication of Helicobacter pylori prior to initiating NSAIDs for pain, and the use of a proton pump inhibitor or misoprostol for gastrointestinal protection in older persons taking nonselective NSAIDs or in patients taking a COX-2 selective inhibitor with aspirin.

The guideline recommends that physicians consider opioid therapy for patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life because of pain. People with continual or frequent daily pain may be treated with around-the-clock, time-contingent dosing aimed at achieving steady-state opioid therapy, said Dr. Perry Fine of the pain management center at the University of Utah, Salt Lake City.

He noted the guideline's caution concerning methadone, and recommended that only clinicians who are well versed in its use and risks initiate and titrate the drug. “That doesn't mean you don't do it,” said Dr. Fine, “but hook yourself up to someone who has a lot of experience in this when you believe this drug is indicated, if you don't already have the experience.”

Methadone-related deaths during pain treatment have risen up to eightfold in the past few years. This is largely because methadone is attractive as a relatively inexpensive drug, but it has an unpredictable and long half-life. That the drug stays active is a blessing, but that quality is also a problem because it accumulates in the body, Dr. Fine said.

Earlier this year, the American Pain Society and the American Academy of Pain Medicine released clinical guidance on the management of opioid therapy for chronic noncancer pain (J. Pain 2009;10:113-30). Like the AGS guidelines, that document stressed the need for clinicians to regularly assess patients for pain intensity, functional status, side effects, and safe and responsible use.

The updated AGS guideline gives new references and discussions on the use and limitations of newer adjuvant, topical, and other drugs for recalcitrant pain.

“Persistent pain isn't a normal part of aging and should not be ignored,” Dr. Cheryl Phillips, AGS president, said in a statement. “As seniors become susceptible to more complex health ailments, the need for a clear and precise pain management plan is key.”

The AGS published its first pain guideline in 1998. To arrive at the 2009 recommendations, a panel of experts conducted a systematic review of 2,400 abstracts and 240 data-based, full-text articles. The panel focused on pharmacotherapy because it is the most common strategy used for pain management among elderly people, as well as the area of greatest risk, said Dr. Bruce Ferrell of the University of California, Los Angeles, who chaired the panel. The 2009 update is to be published in an upcoming issue of the Journal of the American Geriatrics Society.

Dr. Katz disclosed that he has served as a paid consultant in the last 12 months for the American Academy of CME Inc. and for UCB Pharma Inc. Dr. Fine said he is a paid consultant or speaker for numerous pharmaceutical companies and has commercial interests in Johnson & Johnson and Cephalon Inc. Dr. Ferrell disclosed no relevant conflict of interest.

Members of the American Geriatric Society panel on the pharmacologic management of persistent pain in older persons include (from left to right) Dr. Bruce Ferrell, Dr. Perry Fine, Dr. James Katz, Dr. F. Michael Gloth III, and Lori Reisner, Pharm.D., shown discussing the release of the guidelines at the AGS annual meeting. Patrice Wendling/Elsevier Global Medical News

CHICAGO — Disease flare rather than infection or treatment complication may explain most cases of macrophage activation syndrome, and the wider use of new biologic agents may significantly reduce its incidence.

Epstein-Barr virus and cytomega-lovirus infections are the most commonly reported causes of macrophage activation syndrome (MAS), and several case reports have implicated gold preparations and sulfa drugs. But most cases of this potentially lethal complication of systemic juvenile idiopathic arthritis (JIA) have remained unexplained, pediatric rheumatologist Alexi Grom said at a symposium sponsored by the American College of Rheumatology.

“If we treat systemic JIA better with new biologics, we are less likely to see MAS because the underlying disease is the setup for this complication,” he said in an interview.

Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic JIA, affecting about 10% of these patients. It may occur at any stage of the disease, even in remission. Recent research suggests that a mild subclinical form of MAS may occur in about 30%-40% of children with active systemic JIA.

“Macrophage activation syndrome is the most devastating aspect” of JIA, Dr. Grom of Cincinnati Children's Hospital Medical Center told the audience.

There are strong clinical similarities between MAS and the genetic disorder familial hemophagocytic lymphohistiocytosis, both of which are characterized by uncontrolled proliferation of T cells and macrophages that exhibit hemophagocytic activity. Recent observations also suggest that dysfunction of the natural killer cell function is relevant to the pathogenesis of both disorders, Dr. Grom said. These cellular abnormalities in MAS patients result in a massive systemic inflammatory response marked by liver dysfunction, cytopenias, and coagulopathy consistent with disseminated intravascular coagulopathy.

The first laboratory signs of MAS are sharp falls in white blood count, hemoglobin count, and platelet count, as well as some evidence of coagulopathy, including a significant elevation of D-dimers and alterations in clotting times. Because liver function is impaired, decreasing serum fibrinogen activity often results in a sharp fall in the erythrocyte sedimentation rate despite persistently elevated C-reactive protein, he said.

Two other important diagnostic features are hypertriglyceridemia, which reflects increased tumor necrosis factor-alpha activity, and extreme hyperferritinemia, with levels of serum ferritin in excess of 10,000 ng/mL in some patients. The diagnosis of MAS is typically confirmed with bone marrow studies, although Dr. Grom noted that abnormalities may not be evident in the early phase. Children with MAS often present with persistent fevers. They usually have enlarged nodes and hepatosplenomegaly, and at later stages bruising, purpura, and mucosal bleeding may be present. In severe cases, there are mental status changes or seizures.

There is no definitive treatment for MAS, but high-dose IV methylprednisolone (30 mg/kg; maximum, 1,000 mg), and cyclosporine oral or IV (2–5 mg/kg) are typically used. If the MAS severity does not lessen with this treatment, clinicians may want to consider chemotherapy with etoposide, which induces apoptosis of various immune cells including macrophages. Data show success with rabbit antithymocyte globulin, which takes aim at the T cells rather than the macrophages (Clin. Immunol. 2009 March 16 [Epub ahead of print]).

Dr. Grom reported no relevant conflicts of interest.

Subclinical MAS may occur in up to 40% of children with active JIA. Its more severe form is devastating. DR. GROM

CHICAGO — Disease flare rather than infection or treatment complication may explain most cases of macrophage activation syndrome, and the wider use of new biologic agents may significantly reduce its incidence.

Epstein-Barr virus and cytomega-lovirus infections are the most commonly reported causes of macrophage activation syndrome (MAS), and several case reports have implicated gold preparations and sulfa drugs. But most cases of this potentially lethal complication of systemic juvenile idiopathic arthritis (JIA) have remained unexplained, pediatric rheumatologist Alexi Grom said at a symposium sponsored by the American College of Rheumatology.

“If we treat systemic JIA better with new biologics, we are less likely to see MAS because the underlying disease is the setup for this complication,” he said in an interview.

Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic JIA, affecting about 10% of these patients. It may occur at any stage of the disease, even in remission. Recent research suggests that a mild subclinical form of MAS may occur in about 30%-40% of children with active systemic JIA.

“Macrophage activation syndrome is the most devastating aspect” of JIA, Dr. Grom of Cincinnati Children's Hospital Medical Center told the audience.

There are strong clinical similarities between MAS and the genetic disorder familial hemophagocytic lymphohistiocytosis, both of which are characterized by uncontrolled proliferation of T cells and macrophages that exhibit hemophagocytic activity. Recent observations also suggest that dysfunction of the natural killer cell function is relevant to the pathogenesis of both disorders, Dr. Grom said. These cellular abnormalities in MAS patients result in a massive systemic inflammatory response marked by liver dysfunction, cytopenias, and coagulopathy consistent with disseminated intravascular coagulopathy.

The first laboratory signs of MAS are sharp falls in white blood count, hemoglobin count, and platelet count, as well as some evidence of coagulopathy, including a significant elevation of D-dimers and alterations in clotting times. Because liver function is impaired, decreasing serum fibrinogen activity often results in a sharp fall in the erythrocyte sedimentation rate despite persistently elevated C-reactive protein, he said.

Two other important diagnostic features are hypertriglyceridemia, which reflects increased tumor necrosis factor-alpha activity, and extreme hyperferritinemia, with levels of serum ferritin in excess of 10,000 ng/mL in some patients. The diagnosis of MAS is typically confirmed with bone marrow studies, although Dr. Grom noted that abnormalities may not be evident in the early phase. Children with MAS often present with persistent fevers. They usually have enlarged nodes and hepatosplenomegaly, and at later stages bruising, purpura, and mucosal bleeding may be present. In severe cases, there are mental status changes or seizures.

There is no definitive treatment for MAS, but high-dose IV methylprednisolone (30 mg/kg; maximum, 1,000 mg), and cyclosporine oral or IV (2–5 mg/kg) are typically used. If the MAS severity does not lessen with this treatment, clinicians may want to consider chemotherapy with etoposide, which induces apoptosis of various immune cells including macrophages. Data show success with rabbit antithymocyte globulin, which takes aim at the T cells rather than the macrophages (Clin. Immunol. 2009 March 16 [Epub ahead of print]).

Dr. Grom reported no relevant conflicts of interest.

Subclinical MAS may occur in up to 40% of children with active JIA. Its more severe form is devastating. DR. GROM

CHICAGO — Disease flare rather than infection or treatment complication may explain most cases of macrophage activation syndrome, and the wider use of new biologic agents may significantly reduce its incidence.

Epstein-Barr virus and cytomega-lovirus infections are the most commonly reported causes of macrophage activation syndrome (MAS), and several case reports have implicated gold preparations and sulfa drugs. But most cases of this potentially lethal complication of systemic juvenile idiopathic arthritis (JIA) have remained unexplained, pediatric rheumatologist Alexi Grom said at a symposium sponsored by the American College of Rheumatology.

“If we treat systemic JIA better with new biologics, we are less likely to see MAS because the underlying disease is the setup for this complication,” he said in an interview.

Although MAS has been reported in association with almost any rheumatic disease, it is by far most common in systemic JIA, affecting about 10% of these patients. It may occur at any stage of the disease, even in remission. Recent research suggests that a mild subclinical form of MAS may occur in about 30%-40% of children with active systemic JIA.

“Macrophage activation syndrome is the most devastating aspect” of JIA, Dr. Grom of Cincinnati Children's Hospital Medical Center told the audience.

There are strong clinical similarities between MAS and the genetic disorder familial hemophagocytic lymphohistiocytosis, both of which are characterized by uncontrolled proliferation of T cells and macrophages that exhibit hemophagocytic activity. Recent observations also suggest that dysfunction of the natural killer cell function is relevant to the pathogenesis of both disorders, Dr. Grom said. These cellular abnormalities in MAS patients result in a massive systemic inflammatory response marked by liver dysfunction, cytopenias, and coagulopathy consistent with disseminated intravascular coagulopathy.

The first laboratory signs of MAS are sharp falls in white blood count, hemoglobin count, and platelet count, as well as some evidence of coagulopathy, including a significant elevation of D-dimers and alterations in clotting times. Because liver function is impaired, decreasing serum fibrinogen activity often results in a sharp fall in the erythrocyte sedimentation rate despite persistently elevated C-reactive protein, he said.

Two other important diagnostic features are hypertriglyceridemia, which reflects increased tumor necrosis factor-alpha activity, and extreme hyperferritinemia, with levels of serum ferritin in excess of 10,000 ng/mL in some patients. The diagnosis of MAS is typically confirmed with bone marrow studies, although Dr. Grom noted that abnormalities may not be evident in the early phase. Children with MAS often present with persistent fevers. They usually have enlarged nodes and hepatosplenomegaly, and at later stages bruising, purpura, and mucosal bleeding may be present. In severe cases, there are mental status changes or seizures.

There is no definitive treatment for MAS, but high-dose IV methylprednisolone (30 mg/kg; maximum, 1,000 mg), and cyclosporine oral or IV (2–5 mg/kg) are typically used. If the MAS severity does not lessen with this treatment, clinicians may want to consider chemotherapy with etoposide, which induces apoptosis of various immune cells including macrophages. Data show success with rabbit antithymocyte globulin, which takes aim at the T cells rather than the macrophages (Clin. Immunol. 2009 March 16 [Epub ahead of print]).

Dr. Grom reported no relevant conflicts of interest.

Subclinical MAS may occur in up to 40% of children with active JIA. Its more severe form is devastating. DR. GROM

Rheumatoid arthritis patients taking tumor necrosis factor inhibitors switch agents often, resulting in low 2-year continuation rates for these agents, despite the fact that no large, controlled studies have been done on the effects of frequent switching.

“Increased expectations on the part of the patient or the physician could play a role in creating impatience when immediate results are not seen” with given anti-TNF inhibitors, wrote Dr. Yusuf Yazici from the New York University Hospital for Joint Diseases, and colleagues.

And although much of the existing literature does support switching to another anti-TNF agent after initial failure, “these results have been reported mostly in small, short-term studies that focus on efficacy outcomes, not TNF inhibitor survival in the 'real world,'” he added.

In a study to assess anti-TNF treatment patterns, Dr. Yazici and colleagues looked at insurance claims data from 90 managed care organizations on 50 million patients in the United States. They analyzed data on all patients with RA who initiated anti-TNF therapy between Jan. 1, 2000, and July 1, 2005. A subsidiary cohort of the 6,070 patients who started an anti-TNF agent between 2003 and 2005 was also analyzed to assess use of adalimumab, which was not commercially available until 2003.

Patients on infliximab had the highest percentage of continuation on the drug in both cohorts. However, at 2 years, this figure was only 50%.

Furthermore, 40% of patients starting on infliximab needed one or more dose escalation over the study period, which has “important implications, given the drugs and administration costs associated with more medication use,” wrote the authors (J. Rheumatol. 2009 March 30 [doi:10.3899/jrheum.080592]).

Additionally, despite the relatively high continuation rate seen with infliximab, the authors found that etanercept was the most commonly prescribed initial anti-TNF agent, used by about 50% of patients in both cohorts who were starting anti-TNF therapy for the first time. However, at 2 years in both cohorts, only about 20% of the initial etanercept patients remained on the drug.

In the subcohort, adalimumab was the initial drug started by 1,365 patients (23% of the cohort); the continuation rates closely mirrored those seen with etanercept.

Dr. Yazici and his colleagues speculated that the flexibility of infliximab scheduling and dosing, and the ability of a majority of patients to increase their dose, may explain why infliximab had higher continuation rates than did the two other agents. Additionally, the authors postulated that because infliximab is an agent that is given by infusion and thus requires regular follow-up, “seeing a physician regularly may encourage a patient to remain” on the regimen.

They recommend that other agents now on the market, like abatacept and rituximab, also be investigated in a real world setting.

“TNF inhibitor use patterns are changing with time, with more frequent changes and shorter duration of treatment before the change,” wrote the authors. “Further research needs to be conducted to determine if those tends remain constant with the availability of new biologic treatment options, and how these newer treatments influence the treatment algorithm.”

Dr. Yazici has served as a consultant and/or speaker for Bristol-Myers Squibb Co., Celgene Corp., Centocor Inc., Genentech Inc., Hoffmann-La Roche Inc., and UCB SA. One of the authors on the current study is an employee of Bristol-Myers Squibb.

Rheumatoid arthritis patients taking tumor necrosis factor inhibitors switch agents often, resulting in low 2-year continuation rates for these agents, despite the fact that no large, controlled studies have been done on the effects of frequent switching.

“Increased expectations on the part of the patient or the physician could play a role in creating impatience when immediate results are not seen” with given anti-TNF inhibitors, wrote Dr. Yusuf Yazici from the New York University Hospital for Joint Diseases, and colleagues.

And although much of the existing literature does support switching to another anti-TNF agent after initial failure, “these results have been reported mostly in small, short-term studies that focus on efficacy outcomes, not TNF inhibitor survival in the 'real world,'” he added.

In a study to assess anti-TNF treatment patterns, Dr. Yazici and colleagues looked at insurance claims data from 90 managed care organizations on 50 million patients in the United States. They analyzed data on all patients with RA who initiated anti-TNF therapy between Jan. 1, 2000, and July 1, 2005. A subsidiary cohort of the 6,070 patients who started an anti-TNF agent between 2003 and 2005 was also analyzed to assess use of adalimumab, which was not commercially available until 2003.

Patients on infliximab had the highest percentage of continuation on the drug in both cohorts. However, at 2 years, this figure was only 50%.

Furthermore, 40% of patients starting on infliximab needed one or more dose escalation over the study period, which has “important implications, given the drugs and administration costs associated with more medication use,” wrote the authors (J. Rheumatol. 2009 March 30 [doi:10.3899/jrheum.080592]).

Additionally, despite the relatively high continuation rate seen with infliximab, the authors found that etanercept was the most commonly prescribed initial anti-TNF agent, used by about 50% of patients in both cohorts who were starting anti-TNF therapy for the first time. However, at 2 years in both cohorts, only about 20% of the initial etanercept patients remained on the drug.

In the subcohort, adalimumab was the initial drug started by 1,365 patients (23% of the cohort); the continuation rates closely mirrored those seen with etanercept.

Dr. Yazici and his colleagues speculated that the flexibility of infliximab scheduling and dosing, and the ability of a majority of patients to increase their dose, may explain why infliximab had higher continuation rates than did the two other agents. Additionally, the authors postulated that because infliximab is an agent that is given by infusion and thus requires regular follow-up, “seeing a physician regularly may encourage a patient to remain” on the regimen.

They recommend that other agents now on the market, like abatacept and rituximab, also be investigated in a real world setting.

“TNF inhibitor use patterns are changing with time, with more frequent changes and shorter duration of treatment before the change,” wrote the authors. “Further research needs to be conducted to determine if those tends remain constant with the availability of new biologic treatment options, and how these newer treatments influence the treatment algorithm.”

Dr. Yazici has served as a consultant and/or speaker for Bristol-Myers Squibb Co., Celgene Corp., Centocor Inc., Genentech Inc., Hoffmann-La Roche Inc., and UCB SA. One of the authors on the current study is an employee of Bristol-Myers Squibb.

Rheumatoid arthritis patients taking tumor necrosis factor inhibitors switch agents often, resulting in low 2-year continuation rates for these agents, despite the fact that no large, controlled studies have been done on the effects of frequent switching.

“Increased expectations on the part of the patient or the physician could play a role in creating impatience when immediate results are not seen” with given anti-TNF inhibitors, wrote Dr. Yusuf Yazici from the New York University Hospital for Joint Diseases, and colleagues.

And although much of the existing literature does support switching to another anti-TNF agent after initial failure, “these results have been reported mostly in small, short-term studies that focus on efficacy outcomes, not TNF inhibitor survival in the 'real world,'” he added.

In a study to assess anti-TNF treatment patterns, Dr. Yazici and colleagues looked at insurance claims data from 90 managed care organizations on 50 million patients in the United States. They analyzed data on all patients with RA who initiated anti-TNF therapy between Jan. 1, 2000, and July 1, 2005. A subsidiary cohort of the 6,070 patients who started an anti-TNF agent between 2003 and 2005 was also analyzed to assess use of adalimumab, which was not commercially available until 2003.

Patients on infliximab had the highest percentage of continuation on the drug in both cohorts. However, at 2 years, this figure was only 50%.

Furthermore, 40% of patients starting on infliximab needed one or more dose escalation over the study period, which has “important implications, given the drugs and administration costs associated with more medication use,” wrote the authors (J. Rheumatol. 2009 March 30 [doi:10.3899/jrheum.080592]).

Additionally, despite the relatively high continuation rate seen with infliximab, the authors found that etanercept was the most commonly prescribed initial anti-TNF agent, used by about 50% of patients in both cohorts who were starting anti-TNF therapy for the first time. However, at 2 years in both cohorts, only about 20% of the initial etanercept patients remained on the drug.

In the subcohort, adalimumab was the initial drug started by 1,365 patients (23% of the cohort); the continuation rates closely mirrored those seen with etanercept.

Dr. Yazici and his colleagues speculated that the flexibility of infliximab scheduling and dosing, and the ability of a majority of patients to increase their dose, may explain why infliximab had higher continuation rates than did the two other agents. Additionally, the authors postulated that because infliximab is an agent that is given by infusion and thus requires regular follow-up, “seeing a physician regularly may encourage a patient to remain” on the regimen.

They recommend that other agents now on the market, like abatacept and rituximab, also be investigated in a real world setting.

“TNF inhibitor use patterns are changing with time, with more frequent changes and shorter duration of treatment before the change,” wrote the authors. “Further research needs to be conducted to determine if those tends remain constant with the availability of new biologic treatment options, and how these newer treatments influence the treatment algorithm.”

Dr. Yazici has served as a consultant and/or speaker for Bristol-Myers Squibb Co., Celgene Corp., Centocor Inc., Genentech Inc., Hoffmann-La Roche Inc., and UCB SA. One of the authors on the current study is an employee of Bristol-Myers Squibb.

Preoperative MRI scanning of the knee in some patients with joint line pain revealed more advanced degenerative disease than was suggested by clinical examination and plain x-rays, judging from findings from a large British series.

In the study of more than 600 patients presenting with knee symptoms, MRI assessment led to a change in the clinical management of 23% of the patients (141 of 618), study investigators reported.

In most of these patients (129 of 141), the scans revealed unexpected chondral surface lesions, unstable meniscal tears, and other pathologies. The purpose of the study was to determine if preoperative MRI assessment of knee pathology after a clinical examination and plain x-rays affects the surgical management of patients with knee pain.

The study had two parts. First, investigators assessed the accuracy of MRI scans for detecting knee cartilage lesions at their institution, Royal Free Hampstead National Health Service (NHS) Trust, London.

They performed MRI scans and arthroscopic exams on 100 randomly selected patients with knee pain. Using arthroscopy as the standard, the researchers found that the MRI scans had an overall sensitivity of 83% and an overall specificity of 94% for the detection of chondral lesions.

In the second part of the study, the researchers enrolled 618 patients with knee pain (316 women, mean age 55 years; 302 men, mean age 45 years).

All participants were initially examined by a clinician for evidence of arthritis or meniscal tears, and had plain x-rays. The clinician recorded the most probable cause of the pain and the likelihood of proceeding to arthroscopy. All the patients had an initial diagnosis of an arthroscopically treatable lesion.

After this initial consultation, the patients underwent an MRI scan.

The patients and their scans were then reviewed by one of two surgeons who specialized in knees.

The analysis showed that the MRI findings matched the clinical diagnosis in 477 (77%) of the 618 patients; the diagnosis was confirmed by subsequent arthroscopy. In the 141 patients whose MRI findings did not match the clinical diagnosis, 77 had chondral lesions that were not suggested by the clinical exam and plain x-rays, 22 had unexpected meniscal tears rather than chondral lesions, 30 had miscellaneous pathologies, and 12 had a normal MRI scan.

As a result of the MRI findings in these patients, the orthopedic surgeons altered their clinical management, wrote the investigators, led by Dr. Arthur Galea of the Royal Free Hampstead NHS Trust (Arthroscopy 2009;25:473-80).

MRI assessment allowed some patients to avoid “unnecessary arthroscopic intervention and improved the quality of life in a subset of patients who underwent an arthroplasty as a primary procedure,” the authors wrote.

“Preoperative MRI identifies a group of patients who have more advanced DJD [degenerative joint disease] than the clinical assessment and the plain radiographs suggest,” the researchers concluded. The use of MRI “would expedite definitive surgery in patients with advanced osteoarthritis on MRI scans,” they wrote.

“A potential source of bias in our study was that the orthopaedic specialist had the opportunity to view the MRI scans at the time of arthroscopy.

Ethical considerations meant that it was not acceptable to blind the knee specialist from viewing the MRI scan,” they wrote.

The authors reported no conflicts of interest.

Preoperative MRI scanning of the knee in some patients with joint line pain revealed more advanced degenerative disease than was suggested by clinical examination and plain x-rays, judging from findings from a large British series.

In the study of more than 600 patients presenting with knee symptoms, MRI assessment led to a change in the clinical management of 23% of the patients (141 of 618), study investigators reported.

In most of these patients (129 of 141), the scans revealed unexpected chondral surface lesions, unstable meniscal tears, and other pathologies. The purpose of the study was to determine if preoperative MRI assessment of knee pathology after a clinical examination and plain x-rays affects the surgical management of patients with knee pain.

The study had two parts. First, investigators assessed the accuracy of MRI scans for detecting knee cartilage lesions at their institution, Royal Free Hampstead National Health Service (NHS) Trust, London.

They performed MRI scans and arthroscopic exams on 100 randomly selected patients with knee pain. Using arthroscopy as the standard, the researchers found that the MRI scans had an overall sensitivity of 83% and an overall specificity of 94% for the detection of chondral lesions.

In the second part of the study, the researchers enrolled 618 patients with knee pain (316 women, mean age 55 years; 302 men, mean age 45 years).

All participants were initially examined by a clinician for evidence of arthritis or meniscal tears, and had plain x-rays. The clinician recorded the most probable cause of the pain and the likelihood of proceeding to arthroscopy. All the patients had an initial diagnosis of an arthroscopically treatable lesion.

After this initial consultation, the patients underwent an MRI scan.

The patients and their scans were then reviewed by one of two surgeons who specialized in knees.

The analysis showed that the MRI findings matched the clinical diagnosis in 477 (77%) of the 618 patients; the diagnosis was confirmed by subsequent arthroscopy. In the 141 patients whose MRI findings did not match the clinical diagnosis, 77 had chondral lesions that were not suggested by the clinical exam and plain x-rays, 22 had unexpected meniscal tears rather than chondral lesions, 30 had miscellaneous pathologies, and 12 had a normal MRI scan.

As a result of the MRI findings in these patients, the orthopedic surgeons altered their clinical management, wrote the investigators, led by Dr. Arthur Galea of the Royal Free Hampstead NHS Trust (Arthroscopy 2009;25:473-80).

MRI assessment allowed some patients to avoid “unnecessary arthroscopic intervention and improved the quality of life in a subset of patients who underwent an arthroplasty as a primary procedure,” the authors wrote.

“Preoperative MRI identifies a group of patients who have more advanced DJD [degenerative joint disease] than the clinical assessment and the plain radiographs suggest,” the researchers concluded. The use of MRI “would expedite definitive surgery in patients with advanced osteoarthritis on MRI scans,” they wrote.

“A potential source of bias in our study was that the orthopaedic specialist had the opportunity to view the MRI scans at the time of arthroscopy.

Ethical considerations meant that it was not acceptable to blind the knee specialist from viewing the MRI scan,” they wrote.

The authors reported no conflicts of interest.

Preoperative MRI scanning of the knee in some patients with joint line pain revealed more advanced degenerative disease than was suggested by clinical examination and plain x-rays, judging from findings from a large British series.

In the study of more than 600 patients presenting with knee symptoms, MRI assessment led to a change in the clinical management of 23% of the patients (141 of 618), study investigators reported.

In most of these patients (129 of 141), the scans revealed unexpected chondral surface lesions, unstable meniscal tears, and other pathologies. The purpose of the study was to determine if preoperative MRI assessment of knee pathology after a clinical examination and plain x-rays affects the surgical management of patients with knee pain.

The study had two parts. First, investigators assessed the accuracy of MRI scans for detecting knee cartilage lesions at their institution, Royal Free Hampstead National Health Service (NHS) Trust, London.

They performed MRI scans and arthroscopic exams on 100 randomly selected patients with knee pain. Using arthroscopy as the standard, the researchers found that the MRI scans had an overall sensitivity of 83% and an overall specificity of 94% for the detection of chondral lesions.

In the second part of the study, the researchers enrolled 618 patients with knee pain (316 women, mean age 55 years; 302 men, mean age 45 years).

All participants were initially examined by a clinician for evidence of arthritis or meniscal tears, and had plain x-rays. The clinician recorded the most probable cause of the pain and the likelihood of proceeding to arthroscopy. All the patients had an initial diagnosis of an arthroscopically treatable lesion.

After this initial consultation, the patients underwent an MRI scan.

The patients and their scans were then reviewed by one of two surgeons who specialized in knees.

The analysis showed that the MRI findings matched the clinical diagnosis in 477 (77%) of the 618 patients; the diagnosis was confirmed by subsequent arthroscopy. In the 141 patients whose MRI findings did not match the clinical diagnosis, 77 had chondral lesions that were not suggested by the clinical exam and plain x-rays, 22 had unexpected meniscal tears rather than chondral lesions, 30 had miscellaneous pathologies, and 12 had a normal MRI scan.

As a result of the MRI findings in these patients, the orthopedic surgeons altered their clinical management, wrote the investigators, led by Dr. Arthur Galea of the Royal Free Hampstead NHS Trust (Arthroscopy 2009;25:473-80).

MRI assessment allowed some patients to avoid “unnecessary arthroscopic intervention and improved the quality of life in a subset of patients who underwent an arthroplasty as a primary procedure,” the authors wrote.

“Preoperative MRI identifies a group of patients who have more advanced DJD [degenerative joint disease] than the clinical assessment and the plain radiographs suggest,” the researchers concluded. The use of MRI “would expedite definitive surgery in patients with advanced osteoarthritis on MRI scans,” they wrote.

“A potential source of bias in our study was that the orthopaedic specialist had the opportunity to view the MRI scans at the time of arthroscopy.

Ethical considerations meant that it was not acceptable to blind the knee specialist from viewing the MRI scan,” they wrote.

The authors reported no conflicts of interest.

CHICAGO — Clinicians need to step up their use of vaccinations as part of an overall plan to reduce the risk of infection in patients with rheumatic disease who receive tumor necrosis factor inhibitors, Dr. John J. Cush said at a symposium sponsored by the American College of Rheumatology.

“We are not as good as we should be [about vaccinations], and they can really have a big impact by preventing serious infections, especially in our immunosuppressed patients,” he said.

Data from pivotal trials show that the risk of serious infectious events with the biologics is two times that with placebo. This trend did not reach statistical significance in many of the studies, but in the real world it becomes significant, said Dr. Cush, director of clinical rheumatology for the Baylor Research Institute and a professor of medicine and rheumatology at Baylor College of Medicine in Dallas.

He suggests that patients with rheumatoid arthritis (RA) should receive the yearly influenza vaccine, and that pneumococcal vaccinations should be given once, with a second dose 5 years later.

Vaccines for meningococcal disease, human papillomavirus, and hepatitis B are needed where exposure is likely, but it is important to avoid live attenuated vaccines.

The package inserts for several TNF inhibitors were also revised in 2007-2008, warning that tuberculosis has been observed with their use. Data from the British Society for Rheumatology Biologics Register on 10,403 patients taking anti-TNF agents and 3,106 patients taking only disease-modifying anti-rheumatic drugs identified 35 cases of tuberculosis, all occurring in patients on anti-TNF agents. The TB rate was 110 per 100,000 patient-years in anti-TNF-treated patients, putting them above the rate for the general U.K. and U.S. populations (6 per 100,000 patient-years) and on par with alcoholics and patients with HIV, Dr. Cush said.

Manufacturers of anti-TNF agents advise clinicians to employ tuberculosis skin testing (purified protein derivative tuberculin) prior to initiating therapy; to monitor for signs and symptoms of TB, even if the initial PPD was negative; and to initiate latent tuberculosis infection (LTBI) treatment prior to TNF therapy.

Dr. Cush suggested that patients with a positive skin test (5 mm or more) or a history of LTBI can be treated with TNF inhibitors immediately after TB therapy with isoniazid is initiated. Moreover, this practice is routine in some RA clinical trials.

Arguments for suspending anti-TNF therapy could include the belief that TB treatment confers protection, or that anti-TNF therapy may increase the potential for toxicity or may cause worsening of latent TB infection before treatment with isoniazid can start working. Dr. Cush contends that there are no data to support waiting, and although toxicity may be an issue, it can be identified early on by lab testing and physician observation. Reactivation of LTBI has not been shown to occur in anti-TNF-treated patients.

To drive home his point, Dr. Cush highlighted a study among Africans with HIV-associated TB in which eight doses of etanercept (25 mg) administered twice weekly beginning on day 4 of TB therapy actually improved TB killing and overall responses, compared with control therapy (AIDS 2004;18:257-64).

Dr. Cush acknowledged that he would not use TNF inhibitors in RA patients who have invasive fungal disease or chronic hepatitis B, or in those infected with atypical mycobacteria. Clinicians should have safeguards and reminders in place to do PPD skin tests in all RA patients prior to TNF-inhibitor therapy and during year 2 (or when TNF-inhibitor therapy is changed), as this will occasionally pick up patients with latent TB who were initially anergic, he said.

There is no added yield to further annual testing, but the PPD skin test can be repeated if the patient has had a recent exposure, has traveled to a high-risk or endemic area, or has signs or symptoms of a mycobacterial infection.

PPD results are notoriously variable depending on who conducts the test, but results are good for 1-2 weeks, Dr. Cush said.

“It's better to have a patient come back late than not at all,” he said. “The best PPD is the one done by you and read by you.”

As an alternative—or in addition—to conventional skin tests, clinicians may want to consider using the QuantiFERON TB test, which was approved by the Food and Drug Administration in 2001 and measures the release of interferon-gamma in whole blood in response to stimulation by a purified protein derivative. Roughly 10% of QuantiFERON testing is indeterminate, but in general, clinicians can “hang their hat on the results,” he said, noting that PPD tests may be positive in those with a history of bacille Calmette-Guérin (BCG) vaccination, whereas QuantiFERON is unaffected by BCG and more truly reflects the likelihood of latent TB infection.

There is no evidence to support the practice of suspending TNF-inhibitor use in the setting of nonserious infections, unless the symptoms or signs are suggestive of a more serious infection, Dr. Cush said.

In a meta-analysis to be presented by colleague Dr. Kathryn Dao at the upcoming European League Against Rheumatism meeting in Copenhagen, the risk for nonserious infections was increased in patients with RA who received adalimumab (odds ratio, 1.39) or infliximab (OR, 1.53), but not etanercept (OR, 0.99).

“The magnitude is small, but we have to be mindful of these very common events and how they can be properly managed in patients receiving biologics,” he said.

Dr. Cush disclosed that he has been an adviser, consultant, or lecturer for Abbott Laboratories, Centocor Inc., Pfizer Inc., Roche, UCB SA, and Wyeth.

He noted he has been a clinical investigator for or received research support from Celgene Corp., Genentech Inc., Pfizer, Roche, UCB, and the Consortium of Rheumatology Researchers of North America.

While patients need flu shots and other regular immunizations, attenuated vaccines should be avoided. DR. CUSH

CHICAGO — Clinicians need to step up their use of vaccinations as part of an overall plan to reduce the risk of infection in patients with rheumatic disease who receive tumor necrosis factor inhibitors, Dr. John J. Cush said at a symposium sponsored by the American College of Rheumatology.

“We are not as good as we should be [about vaccinations], and they can really have a big impact by preventing serious infections, especially in our immunosuppressed patients,” he said.

Data from pivotal trials show that the risk of serious infectious events with the biologics is two times that with placebo. This trend did not reach statistical significance in many of the studies, but in the real world it becomes significant, said Dr. Cush, director of clinical rheumatology for the Baylor Research Institute and a professor of medicine and rheumatology at Baylor College of Medicine in Dallas.

He suggests that patients with rheumatoid arthritis (RA) should receive the yearly influenza vaccine, and that pneumococcal vaccinations should be given once, with a second dose 5 years later.

Vaccines for meningococcal disease, human papillomavirus, and hepatitis B are needed where exposure is likely, but it is important to avoid live attenuated vaccines.

The package inserts for several TNF inhibitors were also revised in 2007-2008, warning that tuberculosis has been observed with their use. Data from the British Society for Rheumatology Biologics Register on 10,403 patients taking anti-TNF agents and 3,106 patients taking only disease-modifying anti-rheumatic drugs identified 35 cases of tuberculosis, all occurring in patients on anti-TNF agents. The TB rate was 110 per 100,000 patient-years in anti-TNF-treated patients, putting them above the rate for the general U.K. and U.S. populations (6 per 100,000 patient-years) and on par with alcoholics and patients with HIV, Dr. Cush said.

Manufacturers of anti-TNF agents advise clinicians to employ tuberculosis skin testing (purified protein derivative tuberculin) prior to initiating therapy; to monitor for signs and symptoms of TB, even if the initial PPD was negative; and to initiate latent tuberculosis infection (LTBI) treatment prior to TNF therapy.

Dr. Cush suggested that patients with a positive skin test (5 mm or more) or a history of LTBI can be treated with TNF inhibitors immediately after TB therapy with isoniazid is initiated. Moreover, this practice is routine in some RA clinical trials.

Arguments for suspending anti-TNF therapy could include the belief that TB treatment confers protection, or that anti-TNF therapy may increase the potential for toxicity or may cause worsening of latent TB infection before treatment with isoniazid can start working. Dr. Cush contends that there are no data to support waiting, and although toxicity may be an issue, it can be identified early on by lab testing and physician observation. Reactivation of LTBI has not been shown to occur in anti-TNF-treated patients.

To drive home his point, Dr. Cush highlighted a study among Africans with HIV-associated TB in which eight doses of etanercept (25 mg) administered twice weekly beginning on day 4 of TB therapy actually improved TB killing and overall responses, compared with control therapy (AIDS 2004;18:257-64).

Dr. Cush acknowledged that he would not use TNF inhibitors in RA patients who have invasive fungal disease or chronic hepatitis B, or in those infected with atypical mycobacteria. Clinicians should have safeguards and reminders in place to do PPD skin tests in all RA patients prior to TNF-inhibitor therapy and during year 2 (or when TNF-inhibitor therapy is changed), as this will occasionally pick up patients with latent TB who were initially anergic, he said.

There is no added yield to further annual testing, but the PPD skin test can be repeated if the patient has had a recent exposure, has traveled to a high-risk or endemic area, or has signs or symptoms of a mycobacterial infection.

PPD results are notoriously variable depending on who conducts the test, but results are good for 1-2 weeks, Dr. Cush said.

“It's better to have a patient come back late than not at all,” he said. “The best PPD is the one done by you and read by you.”

As an alternative—or in addition—to conventional skin tests, clinicians may want to consider using the QuantiFERON TB test, which was approved by the Food and Drug Administration in 2001 and measures the release of interferon-gamma in whole blood in response to stimulation by a purified protein derivative. Roughly 10% of QuantiFERON testing is indeterminate, but in general, clinicians can “hang their hat on the results,” he said, noting that PPD tests may be positive in those with a history of bacille Calmette-Guérin (BCG) vaccination, whereas QuantiFERON is unaffected by BCG and more truly reflects the likelihood of latent TB infection.

There is no evidence to support the practice of suspending TNF-inhibitor use in the setting of nonserious infections, unless the symptoms or signs are suggestive of a more serious infection, Dr. Cush said.

In a meta-analysis to be presented by colleague Dr. Kathryn Dao at the upcoming European League Against Rheumatism meeting in Copenhagen, the risk for nonserious infections was increased in patients with RA who received adalimumab (odds ratio, 1.39) or infliximab (OR, 1.53), but not etanercept (OR, 0.99).

“The magnitude is small, but we have to be mindful of these very common events and how they can be properly managed in patients receiving biologics,” he said.

Dr. Cush disclosed that he has been an adviser, consultant, or lecturer for Abbott Laboratories, Centocor Inc., Pfizer Inc., Roche, UCB SA, and Wyeth.

He noted he has been a clinical investigator for or received research support from Celgene Corp., Genentech Inc., Pfizer, Roche, UCB, and the Consortium of Rheumatology Researchers of North America.

While patients need flu shots and other regular immunizations, attenuated vaccines should be avoided. DR. CUSH

CHICAGO — Clinicians need to step up their use of vaccinations as part of an overall plan to reduce the risk of infection in patients with rheumatic disease who receive tumor necrosis factor inhibitors, Dr. John J. Cush said at a symposium sponsored by the American College of Rheumatology.

“We are not as good as we should be [about vaccinations], and they can really have a big impact by preventing serious infections, especially in our immunosuppressed patients,” he said.

Data from pivotal trials show that the risk of serious infectious events with the biologics is two times that with placebo. This trend did not reach statistical significance in many of the studies, but in the real world it becomes significant, said Dr. Cush, director of clinical rheumatology for the Baylor Research Institute and a professor of medicine and rheumatology at Baylor College of Medicine in Dallas.

He suggests that patients with rheumatoid arthritis (RA) should receive the yearly influenza vaccine, and that pneumococcal vaccinations should be given once, with a second dose 5 years later.

Vaccines for meningococcal disease, human papillomavirus, and hepatitis B are needed where exposure is likely, but it is important to avoid live attenuated vaccines.

The package inserts for several TNF inhibitors were also revised in 2007-2008, warning that tuberculosis has been observed with their use. Data from the British Society for Rheumatology Biologics Register on 10,403 patients taking anti-TNF agents and 3,106 patients taking only disease-modifying anti-rheumatic drugs identified 35 cases of tuberculosis, all occurring in patients on anti-TNF agents. The TB rate was 110 per 100,000 patient-years in anti-TNF-treated patients, putting them above the rate for the general U.K. and U.S. populations (6 per 100,000 patient-years) and on par with alcoholics and patients with HIV, Dr. Cush said.

Manufacturers of anti-TNF agents advise clinicians to employ tuberculosis skin testing (purified protein derivative tuberculin) prior to initiating therapy; to monitor for signs and symptoms of TB, even if the initial PPD was negative; and to initiate latent tuberculosis infection (LTBI) treatment prior to TNF therapy.

Dr. Cush suggested that patients with a positive skin test (5 mm or more) or a history of LTBI can be treated with TNF inhibitors immediately after TB therapy with isoniazid is initiated. Moreover, this practice is routine in some RA clinical trials.

Arguments for suspending anti-TNF therapy could include the belief that TB treatment confers protection, or that anti-TNF therapy may increase the potential for toxicity or may cause worsening of latent TB infection before treatment with isoniazid can start working. Dr. Cush contends that there are no data to support waiting, and although toxicity may be an issue, it can be identified early on by lab testing and physician observation. Reactivation of LTBI has not been shown to occur in anti-TNF-treated patients.

To drive home his point, Dr. Cush highlighted a study among Africans with HIV-associated TB in which eight doses of etanercept (25 mg) administered twice weekly beginning on day 4 of TB therapy actually improved TB killing and overall responses, compared with control therapy (AIDS 2004;18:257-64).

Dr. Cush acknowledged that he would not use TNF inhibitors in RA patients who have invasive fungal disease or chronic hepatitis B, or in those infected with atypical mycobacteria. Clinicians should have safeguards and reminders in place to do PPD skin tests in all RA patients prior to TNF-inhibitor therapy and during year 2 (or when TNF-inhibitor therapy is changed), as this will occasionally pick up patients with latent TB who were initially anergic, he said.

There is no added yield to further annual testing, but the PPD skin test can be repeated if the patient has had a recent exposure, has traveled to a high-risk or endemic area, or has signs or symptoms of a mycobacterial infection.

PPD results are notoriously variable depending on who conducts the test, but results are good for 1-2 weeks, Dr. Cush said.

“It's better to have a patient come back late than not at all,” he said. “The best PPD is the one done by you and read by you.”

As an alternative—or in addition—to conventional skin tests, clinicians may want to consider using the QuantiFERON TB test, which was approved by the Food and Drug Administration in 2001 and measures the release of interferon-gamma in whole blood in response to stimulation by a purified protein derivative. Roughly 10% of QuantiFERON testing is indeterminate, but in general, clinicians can “hang their hat on the results,” he said, noting that PPD tests may be positive in those with a history of bacille Calmette-Guérin (BCG) vaccination, whereas QuantiFERON is unaffected by BCG and more truly reflects the likelihood of latent TB infection.

There is no evidence to support the practice of suspending TNF-inhibitor use in the setting of nonserious infections, unless the symptoms or signs are suggestive of a more serious infection, Dr. Cush said.

In a meta-analysis to be presented by colleague Dr. Kathryn Dao at the upcoming European League Against Rheumatism meeting in Copenhagen, the risk for nonserious infections was increased in patients with RA who received adalimumab (odds ratio, 1.39) or infliximab (OR, 1.53), but not etanercept (OR, 0.99).

“The magnitude is small, but we have to be mindful of these very common events and how they can be properly managed in patients receiving biologics,” he said.

Dr. Cush disclosed that he has been an adviser, consultant, or lecturer for Abbott Laboratories, Centocor Inc., Pfizer Inc., Roche, UCB SA, and Wyeth.

He noted he has been a clinical investigator for or received research support from Celgene Corp., Genentech Inc., Pfizer, Roche, UCB, and the Consortium of Rheumatology Researchers of North America.

While patients need flu shots and other regular immunizations, attenuated vaccines should be avoided. DR. CUSH

The combination of the connective tissue diseases questionnaire plus rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity had a 95% sensitivity and 32% specificity for identifying people with at least one swollen joint at free community health fairs.

The study, presented at the Western regional meeting of the American Federation for Medical Research, is one of few to examine rheumatoid arthritis screening techniques in the community health fair setting, where more prevalent conditions, such as diabetes and hypertension, receive more attention. The nonprofit 9Health administers volunteer-driven health fairs in Colorado that offer a variety of free or low-cost screenings to more than 90,000 people per year.

In all, 601 participants (16% of total attendees) were screened at five sites in the Denver area. The researchers administered the 30-item questionnaire (Ann. Epidemiol. 1995;5:297-302) as well as blood tests for rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP). The patients' joints were examined by a rheumatologist who was unaware of the assay and questionnaire results.

Of those screened, 84 people (14%) had one or more swollen joints that would be consistent with possible inflammatory arthritis, said Dr. Kevin Deane of the division of rheumatology of the University of Colorado, Denver. “Nine met at least four ACR criteria for RA but never had a prior diagnosis,” he said in an interview.

“An additional 15 people had a swollen joint and RF or CCP positivity, but met fewer than four ACR RA criteria. They may have early RA,” he added. And another 41 people had either RF or anti-CCP positivity but didn't have any arthritis. “So something is going on immunologically, but no arthritis yet,” he said.

“The importance of identifying RA early is growing,” Dr. Deane said, but finding people with early disease remains difficult. “We thought we would try to utilize the health fair to screen a pretty large population.”

The cost of the screening effort is $42 per person screened, which does not include salaries because the study relied on volunteers. “If you count person-hours into this, this health fair screen cost about $2,000 to identify each person with RA or inflammatory arthritis,” said Dr. Deane.

“What we don't know is, is that worth it? We think so; if you identify and treat RA early, you should reduce disability and lost work time. More study is needed to find out the true cost/benefit of this approach,” he said.

A follow-up study aiming to screen 5,000 health fair attendees is planned for later this year. Abbott Laboratories supported the cost of screening and assays, and was a cosponsor of the 9Health Fair, along with Quest Diagnostics Inc. and GE Healthcare. The authors disclosed no relevant conflicts of interest.

The combination of the connective tissue diseases questionnaire plus rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity had a 95% sensitivity and 32% specificity for identifying people with at least one swollen joint at free community health fairs.

The study, presented at the Western regional meeting of the American Federation for Medical Research, is one of few to examine rheumatoid arthritis screening techniques in the community health fair setting, where more prevalent conditions, such as diabetes and hypertension, receive more attention. The nonprofit 9Health administers volunteer-driven health fairs in Colorado that offer a variety of free or low-cost screenings to more than 90,000 people per year.

In all, 601 participants (16% of total attendees) were screened at five sites in the Denver area. The researchers administered the 30-item questionnaire (Ann. Epidemiol. 1995;5:297-302) as well as blood tests for rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP). The patients' joints were examined by a rheumatologist who was unaware of the assay and questionnaire results.

Of those screened, 84 people (14%) had one or more swollen joints that would be consistent with possible inflammatory arthritis, said Dr. Kevin Deane of the division of rheumatology of the University of Colorado, Denver. “Nine met at least four ACR criteria for RA but never had a prior diagnosis,” he said in an interview.

“An additional 15 people had a swollen joint and RF or CCP positivity, but met fewer than four ACR RA criteria. They may have early RA,” he added. And another 41 people had either RF or anti-CCP positivity but didn't have any arthritis. “So something is going on immunologically, but no arthritis yet,” he said.

“The importance of identifying RA early is growing,” Dr. Deane said, but finding people with early disease remains difficult. “We thought we would try to utilize the health fair to screen a pretty large population.”

The cost of the screening effort is $42 per person screened, which does not include salaries because the study relied on volunteers. “If you count person-hours into this, this health fair screen cost about $2,000 to identify each person with RA or inflammatory arthritis,” said Dr. Deane.

“What we don't know is, is that worth it? We think so; if you identify and treat RA early, you should reduce disability and lost work time. More study is needed to find out the true cost/benefit of this approach,” he said.

A follow-up study aiming to screen 5,000 health fair attendees is planned for later this year. Abbott Laboratories supported the cost of screening and assays, and was a cosponsor of the 9Health Fair, along with Quest Diagnostics Inc. and GE Healthcare. The authors disclosed no relevant conflicts of interest.

The combination of the connective tissue diseases questionnaire plus rheumatoid factor and anti-cyclic citrullinated peptide antibody positivity had a 95% sensitivity and 32% specificity for identifying people with at least one swollen joint at free community health fairs.

The study, presented at the Western regional meeting of the American Federation for Medical Research, is one of few to examine rheumatoid arthritis screening techniques in the community health fair setting, where more prevalent conditions, such as diabetes and hypertension, receive more attention. The nonprofit 9Health administers volunteer-driven health fairs in Colorado that offer a variety of free or low-cost screenings to more than 90,000 people per year.

In all, 601 participants (16% of total attendees) were screened at five sites in the Denver area. The researchers administered the 30-item questionnaire (Ann. Epidemiol. 1995;5:297-302) as well as blood tests for rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP). The patients' joints were examined by a rheumatologist who was unaware of the assay and questionnaire results.

Of those screened, 84 people (14%) had one or more swollen joints that would be consistent with possible inflammatory arthritis, said Dr. Kevin Deane of the division of rheumatology of the University of Colorado, Denver. “Nine met at least four ACR criteria for RA but never had a prior diagnosis,” he said in an interview.

“An additional 15 people had a swollen joint and RF or CCP positivity, but met fewer than four ACR RA criteria. They may have early RA,” he added. And another 41 people had either RF or anti-CCP positivity but didn't have any arthritis. “So something is going on immunologically, but no arthritis yet,” he said.

“The importance of identifying RA early is growing,” Dr. Deane said, but finding people with early disease remains difficult. “We thought we would try to utilize the health fair to screen a pretty large population.”

The cost of the screening effort is $42 per person screened, which does not include salaries because the study relied on volunteers. “If you count person-hours into this, this health fair screen cost about $2,000 to identify each person with RA or inflammatory arthritis,” said Dr. Deane.

“What we don't know is, is that worth it? We think so; if you identify and treat RA early, you should reduce disability and lost work time. More study is needed to find out the true cost/benefit of this approach,” he said.

A follow-up study aiming to screen 5,000 health fair attendees is planned for later this year. Abbott Laboratories supported the cost of screening and assays, and was a cosponsor of the 9Health Fair, along with Quest Diagnostics Inc. and GE Healthcare. The authors disclosed no relevant conflicts of interest.

NEW YORK — Patients with rheumatoid arthritis and elevated C-reactive protein levels may benefit from treatment with a statin to lower their CRP levels and consequently their risk for a cardiovascular event, regardless of their cholesterol levels, according to Dr. Jeffrey Greenberg.

This insight comes from a review of data from the 2008 JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) study of almost 18,000 people, all of whom had high-sensitivity CRP (hs-CRP) levels above 2 mg/L, but relatively normal LDL cholesterol levels of less than 130 mg/dL. They were randomized to either 20 mg rosuvastatin or placebo.

The trial planned to run 5 years; however, it was stopped after 2 years when the statin dropped LDL cholesterol levels by 50% on average, while CRP levels dropped by 37%. Of clinical note, the patients on the statin had significantly fewer episodes of nonfatal myocardial infarction, any MI, nonfatal stroke, and any stroke (N. Engl. J. Med. 2008;359:2195-207).

Although strictly speaking one might say that the findings from JUPITER cannot be extrapolated to rheumatoid arthritis patients, “clinical trials of this magnitude are rarely conducted in RA populations,” noted Dr. Greenberg. Rheumatologists need to extrapolate what they can from such large and potentially applicable trials, as well as from available and relevant observational studies.

Another compelling finding concerning the role of hs-CRP in increasing heart disease risk emerged after Dr. Greenberg's presentation: It was reported from the American College of Cardiology's annual meeting that JUPITER investigators doing subset analysis said that the effect of the statin on lowering the risk for cardiac events stemmed from its hs-CRP-lowering properties, rather than from its effect on cholesterol.

During his presentation, Dr. Greenberg, a rheumatologist at New York University Medical Center, reviewed an earlier trial's findings suggesting that statins can act like a disease-modifying antirheumatic drug in RA. TARA (Trial of Atorvastatin in Rheumatoid Arthritis) involved 116 patients, randomized to placebo or 40 mg atorvastatin for 6 months. All patients were on DMARD therapy and some were taking a corticosteroid. Use of a statin reduced all components of their disease activity score, including erythrocyte sedimentation rate, hs-CRP level, swollen joint count, and plasma viscosity. About 30% of patients had a 50% reduction in their CRP (Lancet 2004;363:2015-21).

Findings from recent studies suggest that RA patients are more likely than other patients with cardiovascular disease to have silent myocardial infarctions and sudden death (Arthritis Rheum. 2005;52:402-11). Another study found that RA patients who present with acute coronary syndrome may be more likely than other patients to have a second event and not to survive it (Ann. Rheum. Dis. 2006;65:348-53).

Given their patients' increased risk for CVD and its propensity for atypical presentation, rheumatologists must increase their vigilance to identify risk factors and intervene to lower them, he said.

NEW YORK — Patients with rheumatoid arthritis and elevated C-reactive protein levels may benefit from treatment with a statin to lower their CRP levels and consequently their risk for a cardiovascular event, regardless of their cholesterol levels, according to Dr. Jeffrey Greenberg.

This insight comes from a review of data from the 2008 JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) study of almost 18,000 people, all of whom had high-sensitivity CRP (hs-CRP) levels above 2 mg/L, but relatively normal LDL cholesterol levels of less than 130 mg/dL. They were randomized to either 20 mg rosuvastatin or placebo.

The trial planned to run 5 years; however, it was stopped after 2 years when the statin dropped LDL cholesterol levels by 50% on average, while CRP levels dropped by 37%. Of clinical note, the patients on the statin had significantly fewer episodes of nonfatal myocardial infarction, any MI, nonfatal stroke, and any stroke (N. Engl. J. Med. 2008;359:2195-207).

Although strictly speaking one might say that the findings from JUPITER cannot be extrapolated to rheumatoid arthritis patients, “clinical trials of this magnitude are rarely conducted in RA populations,” noted Dr. Greenberg. Rheumatologists need to extrapolate what they can from such large and potentially applicable trials, as well as from available and relevant observational studies.

Another compelling finding concerning the role of hs-CRP in increasing heart disease risk emerged after Dr. Greenberg's presentation: It was reported from the American College of Cardiology's annual meeting that JUPITER investigators doing subset analysis said that the effect of the statin on lowering the risk for cardiac events stemmed from its hs-CRP-lowering properties, rather than from its effect on cholesterol.

During his presentation, Dr. Greenberg, a rheumatologist at New York University Medical Center, reviewed an earlier trial's findings suggesting that statins can act like a disease-modifying antirheumatic drug in RA. TARA (Trial of Atorvastatin in Rheumatoid Arthritis) involved 116 patients, randomized to placebo or 40 mg atorvastatin for 6 months. All patients were on DMARD therapy and some were taking a corticosteroid. Use of a statin reduced all components of their disease activity score, including erythrocyte sedimentation rate, hs-CRP level, swollen joint count, and plasma viscosity. About 30% of patients had a 50% reduction in their CRP (Lancet 2004;363:2015-21).

Findings from recent studies suggest that RA patients are more likely than other patients with cardiovascular disease to have silent myocardial infarctions and sudden death (Arthritis Rheum. 2005;52:402-11). Another study found that RA patients who present with acute coronary syndrome may be more likely than other patients to have a second event and not to survive it (Ann. Rheum. Dis. 2006;65:348-53).

Given their patients' increased risk for CVD and its propensity for atypical presentation, rheumatologists must increase their vigilance to identify risk factors and intervene to lower them, he said.

NEW YORK — Patients with rheumatoid arthritis and elevated C-reactive protein levels may benefit from treatment with a statin to lower their CRP levels and consequently their risk for a cardiovascular event, regardless of their cholesterol levels, according to Dr. Jeffrey Greenberg.

This insight comes from a review of data from the 2008 JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) study of almost 18,000 people, all of whom had high-sensitivity CRP (hs-CRP) levels above 2 mg/L, but relatively normal LDL cholesterol levels of less than 130 mg/dL. They were randomized to either 20 mg rosuvastatin or placebo.

The trial planned to run 5 years; however, it was stopped after 2 years when the statin dropped LDL cholesterol levels by 50% on average, while CRP levels dropped by 37%. Of clinical note, the patients on the statin had significantly fewer episodes of nonfatal myocardial infarction, any MI, nonfatal stroke, and any stroke (N. Engl. J. Med. 2008;359:2195-207).

Although strictly speaking one might say that the findings from JUPITER cannot be extrapolated to rheumatoid arthritis patients, “clinical trials of this magnitude are rarely conducted in RA populations,” noted Dr. Greenberg. Rheumatologists need to extrapolate what they can from such large and potentially applicable trials, as well as from available and relevant observational studies.

Another compelling finding concerning the role of hs-CRP in increasing heart disease risk emerged after Dr. Greenberg's presentation: It was reported from the American College of Cardiology's annual meeting that JUPITER investigators doing subset analysis said that the effect of the statin on lowering the risk for cardiac events stemmed from its hs-CRP-lowering properties, rather than from its effect on cholesterol.

During his presentation, Dr. Greenberg, a rheumatologist at New York University Medical Center, reviewed an earlier trial's findings suggesting that statins can act like a disease-modifying antirheumatic drug in RA. TARA (Trial of Atorvastatin in Rheumatoid Arthritis) involved 116 patients, randomized to placebo or 40 mg atorvastatin for 6 months. All patients were on DMARD therapy and some were taking a corticosteroid. Use of a statin reduced all components of their disease activity score, including erythrocyte sedimentation rate, hs-CRP level, swollen joint count, and plasma viscosity. About 30% of patients had a 50% reduction in their CRP (Lancet 2004;363:2015-21).

Findings from recent studies suggest that RA patients are more likely than other patients with cardiovascular disease to have silent myocardial infarctions and sudden death (Arthritis Rheum. 2005;52:402-11). Another study found that RA patients who present with acute coronary syndrome may be more likely than other patients to have a second event and not to survive it (Ann. Rheum. Dis. 2006;65:348-53).

Given their patients' increased risk for CVD and its propensity for atypical presentation, rheumatologists must increase their vigilance to identify risk factors and intervene to lower them, he said.

More than half of adults with heart disease also had arthritis, and they were 30% more likely to be physically inactive than were those with heart disease alone, judging from the findings of a survey of 757,959 Americans.

The Centers for Disease Control and Prevention analyzed data from all 50 states in the 2005 and 2007 Behavioral Risk Factor Surveillance System. In telephone interviews, 3% of respondents said they had been diagnosed with heart disease alone, 23% reported a diagnosis of arthritis alone, 4% said they had both, and 70% had neither.

Arthritis—defined as arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia—was present in 57% of the respondents with heart disease, compared with 27% of the total population (MMWR 2009;58:165-9).

In an interview, rheumatologist John A. Goldman, who was not involved with this study, said that getting patients with joint pain to increase activity is a priority for his colleagues who treat arthritis. “The CDC's recent slogan is 'Exercise, the Arthritis Pain Reliever.' Exercise is necessary. Working with physical therapists—especially trainers—on weight reduction; nonimpact, loading exercises; [and] bracing” can all help, said Dr. Goldman, who has a private rheumatology practice in Atlanta.

The investigators asked six questions about the frequency and duration of nonoccupational activities of moderate and vigorous activity; respondents who reported no participation in such activities were considered to be inactive.

People with heart disease and arthritis had the highest rate of inactivity (29%) compared with rates of 21% in people with heart disease alone, 18% in people with arthritis alone, and 11% in those who had neither heart disease nor arthritis, according to the MMWR report.

After adjustment for the effects of age, sex, education level, body mass index, and race or ethnicity, inactivity was 30% more likely in those with heart disease and arthritis, compared with people who had heart disease alone.

The risk of having one or both conditions increased with age. Men had a higher prevalence of heart disease alone (4%) or heart disease plus arthritis (4%) compared with women (2% and 3.5%, respectively). Women were more likely to have arthritis alone (27%) compared with men (19%). Whites were more likely than blacks to have one or both conditions. Each of these comparisons between subgroups was statistically significant.

According to Dr. Goldman, treating arthritis patients who are at risk for heart disease requires coordination with the patient's cardiologist and/or primary care physician. The use of anti-inflammatory disease-modifying antirheumatic drugs and also biologic therapies like methotrexate and tumor necrosis factor-alpha inhibitors decrease the risk of vascular disease, as do traditional cardiovascular drugs like statins, he said. Thus, treatment of both the RA and other inflammatory diseases, and also treatment for lipids, blood pressure, and diabetes mellitus need to be done in concert, he noted.

Associate Editor Denise Napoli contributed to this article.

ELSEVIER GLOBAL MEDICAL NEWS

More than half of adults with heart disease also had arthritis, and they were 30% more likely to be physically inactive than were those with heart disease alone, judging from the findings of a survey of 757,959 Americans.

The Centers for Disease Control and Prevention analyzed data from all 50 states in the 2005 and 2007 Behavioral Risk Factor Surveillance System. In telephone interviews, 3% of respondents said they had been diagnosed with heart disease alone, 23% reported a diagnosis of arthritis alone, 4% said they had both, and 70% had neither.

Arthritis—defined as arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia—was present in 57% of the respondents with heart disease, compared with 27% of the total population (MMWR 2009;58:165-9).

In an interview, rheumatologist John A. Goldman, who was not involved with this study, said that getting patients with joint pain to increase activity is a priority for his colleagues who treat arthritis. “The CDC's recent slogan is 'Exercise, the Arthritis Pain Reliever.' Exercise is necessary. Working with physical therapists—especially trainers—on weight reduction; nonimpact, loading exercises; [and] bracing” can all help, said Dr. Goldman, who has a private rheumatology practice in Atlanta.

The investigators asked six questions about the frequency and duration of nonoccupational activities of moderate and vigorous activity; respondents who reported no participation in such activities were considered to be inactive.

People with heart disease and arthritis had the highest rate of inactivity (29%) compared with rates of 21% in people with heart disease alone, 18% in people with arthritis alone, and 11% in those who had neither heart disease nor arthritis, according to the MMWR report.

After adjustment for the effects of age, sex, education level, body mass index, and race or ethnicity, inactivity was 30% more likely in those with heart disease and arthritis, compared with people who had heart disease alone.

The risk of having one or both conditions increased with age. Men had a higher prevalence of heart disease alone (4%) or heart disease plus arthritis (4%) compared with women (2% and 3.5%, respectively). Women were more likely to have arthritis alone (27%) compared with men (19%). Whites were more likely than blacks to have one or both conditions. Each of these comparisons between subgroups was statistically significant.

According to Dr. Goldman, treating arthritis patients who are at risk for heart disease requires coordination with the patient's cardiologist and/or primary care physician. The use of anti-inflammatory disease-modifying antirheumatic drugs and also biologic therapies like methotrexate and tumor necrosis factor-alpha inhibitors decrease the risk of vascular disease, as do traditional cardiovascular drugs like statins, he said. Thus, treatment of both the RA and other inflammatory diseases, and also treatment for lipids, blood pressure, and diabetes mellitus need to be done in concert, he noted.

Associate Editor Denise Napoli contributed to this article.

ELSEVIER GLOBAL MEDICAL NEWS

More than half of adults with heart disease also had arthritis, and they were 30% more likely to be physically inactive than were those with heart disease alone, judging from the findings of a survey of 757,959 Americans.

The Centers for Disease Control and Prevention analyzed data from all 50 states in the 2005 and 2007 Behavioral Risk Factor Surveillance System. In telephone interviews, 3% of respondents said they had been diagnosed with heart disease alone, 23% reported a diagnosis of arthritis alone, 4% said they had both, and 70% had neither.

Arthritis—defined as arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia—was present in 57% of the respondents with heart disease, compared with 27% of the total population (MMWR 2009;58:165-9).

In an interview, rheumatologist John A. Goldman, who was not involved with this study, said that getting patients with joint pain to increase activity is a priority for his colleagues who treat arthritis. “The CDC's recent slogan is 'Exercise, the Arthritis Pain Reliever.' Exercise is necessary. Working with physical therapists—especially trainers—on weight reduction; nonimpact, loading exercises; [and] bracing” can all help, said Dr. Goldman, who has a private rheumatology practice in Atlanta.

The investigators asked six questions about the frequency and duration of nonoccupational activities of moderate and vigorous activity; respondents who reported no participation in such activities were considered to be inactive.

People with heart disease and arthritis had the highest rate of inactivity (29%) compared with rates of 21% in people with heart disease alone, 18% in people with arthritis alone, and 11% in those who had neither heart disease nor arthritis, according to the MMWR report.

After adjustment for the effects of age, sex, education level, body mass index, and race or ethnicity, inactivity was 30% more likely in those with heart disease and arthritis, compared with people who had heart disease alone.

The risk of having one or both conditions increased with age. Men had a higher prevalence of heart disease alone (4%) or heart disease plus arthritis (4%) compared with women (2% and 3.5%, respectively). Women were more likely to have arthritis alone (27%) compared with men (19%). Whites were more likely than blacks to have one or both conditions. Each of these comparisons between subgroups was statistically significant.

According to Dr. Goldman, treating arthritis patients who are at risk for heart disease requires coordination with the patient's cardiologist and/or primary care physician. The use of anti-inflammatory disease-modifying antirheumatic drugs and also biologic therapies like methotrexate and tumor necrosis factor-alpha inhibitors decrease the risk of vascular disease, as do traditional cardiovascular drugs like statins, he said. Thus, treatment of both the RA and other inflammatory diseases, and also treatment for lipids, blood pressure, and diabetes mellitus need to be done in concert, he noted.

Associate Editor Denise Napoli contributed to this article.

ELSEVIER GLOBAL MEDICAL NEWS