Rheumatoid Arthritis

Arthritis creates work limitations for about a third of working-age adults with the disease, impacting nearly 7% of the total U.S. workforce, according to a state-by-state study by the Centers for Disease Control.

The first-of-its-kind survey, drawing on data from the Behavioral Risk Factor Surveillance System, may foreshadow a profound challenge to the economy as the population ages. Arthritis today affects 46 million Americans, with an estimated economic toll of $128 billion a year, according to the Arthritis Foundation.

The random digit-dialed telephone survey of more than 200,000 households queried working-age adults in every state, Washington, Guam, Puerto Rico, and the U.S. Virgin Islands about whether they had been diagnosed with arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Respondents with arthritis were asked whether arthritis or joint symptoms affected whether they were employed and the type and amount of work they could do.

The responses are weighted to represent the adult population in each state.

A high degree of variability was found in the state-specific prevalence of arthritis-related work limitations among all adults 18–64 years of age, from 3.4% of adults in Hawaii to 15% in Kentucky, reported Kristina A. Theis and associates at the National Center for Chronic Disease Prevention and the National Center on Birth Defects and Developmental Disability at the CDC (MMWR 2007;56:1045–9).

Among adults with diagnosed arthritis and related conditions, work limitations were reported by a median 33%, from 25.1% in Nevada to 51.3% in Kentucky.

“That's huge,” said Ms. Theis in a telephone interview. “In Kentucky, that represents every other person with arthritis a doctor might be seeing.”

Preventing or minimizing work-related limitations through timely therapy, rehabilitation, and workplace accommodation impacts not only the economy as a whole, but the patients' independence, self-esteem, and financial well-being, she stressed.

“It is not always on the physicians' radar screen to inquire, 'How's your function? How's your pain? And by the way, how is that function and pain impacting you at work?'” said Ms. Theis.

Rheumatologists in the states bookending the new statistics said patient characteristics and availability of services may play into differences seen across states.

In Elizabethtown, Ken., rheumatologist Dr. Daksha Mehta said that some patients travel more than 100 miles to see her. And although there is a nationwide shortage of board-certified rheumatologists, “I'm sure it's worse in Kentucky,” she said.

Access to medical specialists, as well as experts in occupational therapy and workplace ergonomics, may be limited in small, isolated rural communities. Additionally, many patients still do not recognize the need for early diagnosis and treatment.

“I have patients with arthritis who are still working at their factory jobs, still farming, but that's with appropriate therapy … optimizing medications, having physical and occupational therapy, doing home strengthening exercises,” said Dr. Mehta of the Center for Arthritis and Osteoporosis.

Rheumatologist Rex Adams of Arthritis Associates of Nevada in Reno said he doubted the types of jobs performed in his state differ much from those practiced in Kentucky, which has doubled the prevalence of work-related limitations reported by working-aged adults with arthritis.

“Mining is big in Nevada, and there are a lot of service industry workers here,” he said. “Maybe it's because we're just good rheumatologists who keep everyone working!” he joked.

Dr. Adams speculated the variation might be explained by systemic factors, like differences in state disability programs, or perhaps populations. Nevada has a “pretty young, healthy population” with a large percentage of workers who recently moved from other locations. Kentucky's population may be older and more stationary.

In both states, rheumatologists said they advocate a team approach to arthritis management, with an emphasis on therapy and lifestyle modifications as well as medication. Occupational and physical therapy are offered on-site in a growing number of group rheumatology practices.

Such trends could make a difference in patients' ability to perform their jobs, said Ms. Theis from the CDC's Division of Adult and Community Health.

Preliminary findings from a separate CDC study build on a growing body of published research suggesting that physician recommendations concerning arthritis management are highly influential in terms of patient behavior, she explained.

When a physician recommends weight loss, an arthritis-focused exercise program, or workplace accommodations in conjunction with the Americans with Disabilities Act, for example, patients are much more likely to attempt to follow that advice.

“We're hoping physicians will say, 'I have a really important voice that carries a lot of weight on a lot of levels,'” said Ms. Theis. “We see them as one of our most important audiences.”

Sometimes, the physician's role on minimizing work limitations is direct, perhaps by prescribing traditional therapy regimens and even biologic therapy.

Other times, a physician may refer a patient to physical or occupational therapy, or to a hand surgeon for a customized thumb or wrist splint that permits normal workplace activities, said Diana Baldwin, an occupational therapist at the Missouri Arthritis Rehabilitation and Training Center.

“We've found that it isn't enough to tell people, 'Cut back on your hours,' or 'Be more flexible,' or 'Don't do things that hurt,'” she said. “For the average working person with arthritis, that is not useful.”

What is useful is when physicians explain to patients that their joints are vulnerable, and provide a rationale to implement protective strategies, she said.

The Missouri Training Center in Columbia is currently completing a federally funded study that has randomized 84 adults with arthritis to receive either written materials about arthritis in the workplace or interventions conducted by Ms. Baldwin in the work setting, be it a manufacturing workshop, business office, or classroom. She has spent 1.5–2 hours interviewing these workers with arthritis and then has studied them as they work, taking pictures that she will later diagram to show movements that stress the joints including twisting, grabbing, reaching, and bending.

She has investigated ergonomic surgical tools to aid an anesthesiologist, adapted the car of a traveling salesman, and added a step stool to ease a manufacturing specialist's reach to a drill press.

Making such changes early on appears to keep people working longer, more effectively, and with less pain, she said.

But economic realities have proved to be a barrier to early workplace interventions. No janitors have agreed to allow Ms. Baldwin to come to their workplaces to identify practices that might be exacerbating their arthritis, for example. “They're not going to expose the fact that they have arthritis on the job,” she said.

Before modification, the low cart height required the worker to bend forward.

The modification of a raised handle decreased painful bending posture.

Unmodified task required static overreaching and bending of the trunk.

Before modification, leaning forward created greater tension on back muscles. PHOTOS COURTESY DIANA BALDWIN

Arthritis creates work limitations for about a third of working-age adults with the disease, impacting nearly 7% of the total U.S. workforce, according to a state-by-state study by the Centers for Disease Control.

The first-of-its-kind survey, drawing on data from the Behavioral Risk Factor Surveillance System, may foreshadow a profound challenge to the economy as the population ages. Arthritis today affects 46 million Americans, with an estimated economic toll of $128 billion a year, according to the Arthritis Foundation.

The random digit-dialed telephone survey of more than 200,000 households queried working-age adults in every state, Washington, Guam, Puerto Rico, and the U.S. Virgin Islands about whether they had been diagnosed with arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Respondents with arthritis were asked whether arthritis or joint symptoms affected whether they were employed and the type and amount of work they could do.

The responses are weighted to represent the adult population in each state.

A high degree of variability was found in the state-specific prevalence of arthritis-related work limitations among all adults 18–64 years of age, from 3.4% of adults in Hawaii to 15% in Kentucky, reported Kristina A. Theis and associates at the National Center for Chronic Disease Prevention and the National Center on Birth Defects and Developmental Disability at the CDC (MMWR 2007;56:1045–9).

Among adults with diagnosed arthritis and related conditions, work limitations were reported by a median 33%, from 25.1% in Nevada to 51.3% in Kentucky.

“That's huge,” said Ms. Theis in a telephone interview. “In Kentucky, that represents every other person with arthritis a doctor might be seeing.”

Preventing or minimizing work-related limitations through timely therapy, rehabilitation, and workplace accommodation impacts not only the economy as a whole, but the patients' independence, self-esteem, and financial well-being, she stressed.

“It is not always on the physicians' radar screen to inquire, 'How's your function? How's your pain? And by the way, how is that function and pain impacting you at work?'” said Ms. Theis.

Rheumatologists in the states bookending the new statistics said patient characteristics and availability of services may play into differences seen across states.

In Elizabethtown, Ken., rheumatologist Dr. Daksha Mehta said that some patients travel more than 100 miles to see her. And although there is a nationwide shortage of board-certified rheumatologists, “I'm sure it's worse in Kentucky,” she said.

Access to medical specialists, as well as experts in occupational therapy and workplace ergonomics, may be limited in small, isolated rural communities. Additionally, many patients still do not recognize the need for early diagnosis and treatment.

“I have patients with arthritis who are still working at their factory jobs, still farming, but that's with appropriate therapy … optimizing medications, having physical and occupational therapy, doing home strengthening exercises,” said Dr. Mehta of the Center for Arthritis and Osteoporosis.

Rheumatologist Rex Adams of Arthritis Associates of Nevada in Reno said he doubted the types of jobs performed in his state differ much from those practiced in Kentucky, which has doubled the prevalence of work-related limitations reported by working-aged adults with arthritis.

“Mining is big in Nevada, and there are a lot of service industry workers here,” he said. “Maybe it's because we're just good rheumatologists who keep everyone working!” he joked.

Dr. Adams speculated the variation might be explained by systemic factors, like differences in state disability programs, or perhaps populations. Nevada has a “pretty young, healthy population” with a large percentage of workers who recently moved from other locations. Kentucky's population may be older and more stationary.

In both states, rheumatologists said they advocate a team approach to arthritis management, with an emphasis on therapy and lifestyle modifications as well as medication. Occupational and physical therapy are offered on-site in a growing number of group rheumatology practices.

Such trends could make a difference in patients' ability to perform their jobs, said Ms. Theis from the CDC's Division of Adult and Community Health.

Preliminary findings from a separate CDC study build on a growing body of published research suggesting that physician recommendations concerning arthritis management are highly influential in terms of patient behavior, she explained.

When a physician recommends weight loss, an arthritis-focused exercise program, or workplace accommodations in conjunction with the Americans with Disabilities Act, for example, patients are much more likely to attempt to follow that advice.

“We're hoping physicians will say, 'I have a really important voice that carries a lot of weight on a lot of levels,'” said Ms. Theis. “We see them as one of our most important audiences.”

Sometimes, the physician's role on minimizing work limitations is direct, perhaps by prescribing traditional therapy regimens and even biologic therapy.

Other times, a physician may refer a patient to physical or occupational therapy, or to a hand surgeon for a customized thumb or wrist splint that permits normal workplace activities, said Diana Baldwin, an occupational therapist at the Missouri Arthritis Rehabilitation and Training Center.

“We've found that it isn't enough to tell people, 'Cut back on your hours,' or 'Be more flexible,' or 'Don't do things that hurt,'” she said. “For the average working person with arthritis, that is not useful.”

What is useful is when physicians explain to patients that their joints are vulnerable, and provide a rationale to implement protective strategies, she said.

The Missouri Training Center in Columbia is currently completing a federally funded study that has randomized 84 adults with arthritis to receive either written materials about arthritis in the workplace or interventions conducted by Ms. Baldwin in the work setting, be it a manufacturing workshop, business office, or classroom. She has spent 1.5–2 hours interviewing these workers with arthritis and then has studied them as they work, taking pictures that she will later diagram to show movements that stress the joints including twisting, grabbing, reaching, and bending.

She has investigated ergonomic surgical tools to aid an anesthesiologist, adapted the car of a traveling salesman, and added a step stool to ease a manufacturing specialist's reach to a drill press.

Making such changes early on appears to keep people working longer, more effectively, and with less pain, she said.

But economic realities have proved to be a barrier to early workplace interventions. No janitors have agreed to allow Ms. Baldwin to come to their workplaces to identify practices that might be exacerbating their arthritis, for example. “They're not going to expose the fact that they have arthritis on the job,” she said.

Before modification, the low cart height required the worker to bend forward.

The modification of a raised handle decreased painful bending posture.

Unmodified task required static overreaching and bending of the trunk.

Before modification, leaning forward created greater tension on back muscles. PHOTOS COURTESY DIANA BALDWIN

Arthritis creates work limitations for about a third of working-age adults with the disease, impacting nearly 7% of the total U.S. workforce, according to a state-by-state study by the Centers for Disease Control.

The first-of-its-kind survey, drawing on data from the Behavioral Risk Factor Surveillance System, may foreshadow a profound challenge to the economy as the population ages. Arthritis today affects 46 million Americans, with an estimated economic toll of $128 billion a year, according to the Arthritis Foundation.

The random digit-dialed telephone survey of more than 200,000 households queried working-age adults in every state, Washington, Guam, Puerto Rico, and the U.S. Virgin Islands about whether they had been diagnosed with arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Respondents with arthritis were asked whether arthritis or joint symptoms affected whether they were employed and the type and amount of work they could do.

The responses are weighted to represent the adult population in each state.

A high degree of variability was found in the state-specific prevalence of arthritis-related work limitations among all adults 18–64 years of age, from 3.4% of adults in Hawaii to 15% in Kentucky, reported Kristina A. Theis and associates at the National Center for Chronic Disease Prevention and the National Center on Birth Defects and Developmental Disability at the CDC (MMWR 2007;56:1045–9).

Among adults with diagnosed arthritis and related conditions, work limitations were reported by a median 33%, from 25.1% in Nevada to 51.3% in Kentucky.

“That's huge,” said Ms. Theis in a telephone interview. “In Kentucky, that represents every other person with arthritis a doctor might be seeing.”

Preventing or minimizing work-related limitations through timely therapy, rehabilitation, and workplace accommodation impacts not only the economy as a whole, but the patients' independence, self-esteem, and financial well-being, she stressed.

“It is not always on the physicians' radar screen to inquire, 'How's your function? How's your pain? And by the way, how is that function and pain impacting you at work?'” said Ms. Theis.

Rheumatologists in the states bookending the new statistics said patient characteristics and availability of services may play into differences seen across states.

In Elizabethtown, Ken., rheumatologist Dr. Daksha Mehta said that some patients travel more than 100 miles to see her. And although there is a nationwide shortage of board-certified rheumatologists, “I'm sure it's worse in Kentucky,” she said.

Access to medical specialists, as well as experts in occupational therapy and workplace ergonomics, may be limited in small, isolated rural communities. Additionally, many patients still do not recognize the need for early diagnosis and treatment.

“I have patients with arthritis who are still working at their factory jobs, still farming, but that's with appropriate therapy … optimizing medications, having physical and occupational therapy, doing home strengthening exercises,” said Dr. Mehta of the Center for Arthritis and Osteoporosis.

Rheumatologist Rex Adams of Arthritis Associates of Nevada in Reno said he doubted the types of jobs performed in his state differ much from those practiced in Kentucky, which has doubled the prevalence of work-related limitations reported by working-aged adults with arthritis.

“Mining is big in Nevada, and there are a lot of service industry workers here,” he said. “Maybe it's because we're just good rheumatologists who keep everyone working!” he joked.

Dr. Adams speculated the variation might be explained by systemic factors, like differences in state disability programs, or perhaps populations. Nevada has a “pretty young, healthy population” with a large percentage of workers who recently moved from other locations. Kentucky's population may be older and more stationary.

In both states, rheumatologists said they advocate a team approach to arthritis management, with an emphasis on therapy and lifestyle modifications as well as medication. Occupational and physical therapy are offered on-site in a growing number of group rheumatology practices.

Such trends could make a difference in patients' ability to perform their jobs, said Ms. Theis from the CDC's Division of Adult and Community Health.

Preliminary findings from a separate CDC study build on a growing body of published research suggesting that physician recommendations concerning arthritis management are highly influential in terms of patient behavior, she explained.

When a physician recommends weight loss, an arthritis-focused exercise program, or workplace accommodations in conjunction with the Americans with Disabilities Act, for example, patients are much more likely to attempt to follow that advice.

“We're hoping physicians will say, 'I have a really important voice that carries a lot of weight on a lot of levels,'” said Ms. Theis. “We see them as one of our most important audiences.”

Sometimes, the physician's role on minimizing work limitations is direct, perhaps by prescribing traditional therapy regimens and even biologic therapy.

Other times, a physician may refer a patient to physical or occupational therapy, or to a hand surgeon for a customized thumb or wrist splint that permits normal workplace activities, said Diana Baldwin, an occupational therapist at the Missouri Arthritis Rehabilitation and Training Center.

“We've found that it isn't enough to tell people, 'Cut back on your hours,' or 'Be more flexible,' or 'Don't do things that hurt,'” she said. “For the average working person with arthritis, that is not useful.”

What is useful is when physicians explain to patients that their joints are vulnerable, and provide a rationale to implement protective strategies, she said.

The Missouri Training Center in Columbia is currently completing a federally funded study that has randomized 84 adults with arthritis to receive either written materials about arthritis in the workplace or interventions conducted by Ms. Baldwin in the work setting, be it a manufacturing workshop, business office, or classroom. She has spent 1.5–2 hours interviewing these workers with arthritis and then has studied them as they work, taking pictures that she will later diagram to show movements that stress the joints including twisting, grabbing, reaching, and bending.

She has investigated ergonomic surgical tools to aid an anesthesiologist, adapted the car of a traveling salesman, and added a step stool to ease a manufacturing specialist's reach to a drill press.

Making such changes early on appears to keep people working longer, more effectively, and with less pain, she said.

But economic realities have proved to be a barrier to early workplace interventions. No janitors have agreed to allow Ms. Baldwin to come to their workplaces to identify practices that might be exacerbating their arthritis, for example. “They're not going to expose the fact that they have arthritis on the job,” she said.

Before modification, the low cart height required the worker to bend forward.

The modification of a raised handle decreased painful bending posture.

Unmodified task required static overreaching and bending of the trunk.

Before modification, leaning forward created greater tension on back muscles. PHOTOS COURTESY DIANA BALDWIN

BARCELONA — Treatment of rheumatoid arthritis with a combination of certolizumab pegol and methotrexate improved symptoms in a significantly greater proportion of patients than methotrexate alone, according to the results of a phase III trial.

In the 52-week, multicenter, randomized, double-blind trial, about 60% of patients who received dosing regimens with either 200 mg or 400 mg of certolizumab pegol (Cimzia) and methotrexate achieved an American College of Rheumatology (ACR) 20 level of response at 24 weeks on an intent-to-treat basis, compared with only 14% of those who received placebo plus methotrexate.

An ACR 20 level of response is achieved when there is 20% improvement in the number of tender and swollen joints as well as a 20% improvement in at least three of five other parameters.

The rheumatoid arthritis patients in the current trial, which was called RAPID 1, had to have had an inadequate response to methotrexate therapy alone for at least 6 months prior to the start of the study, Dr. Edward C. Keystone reported at the annual European Congress of Rheumatology.

Certolizumab pegol is a humanized monoclonal Fab' fragment conjugated to polyethylene glycol, which prolongs the amount of time that the drug remains in the bloodstream.

It is the first anti-tumor necrosis factor-α drug to be constructed without the Fc fusion protein, which may cause adverse effects in other anti-TNF-α agents.

The drug also is produced in bacteria rather than in Chinese hamster ovary cells said Dr. Keystone, director of the Rebecca MacDonald Centre for Arthritis and Autoimmune Disease at the University of Toronto.

He has received research funds from and has been a consultant for the biopharmaceutical company Union Chimique Belge (UCB), which funded the study.

The RAPID 1 trial tested the lyophilized formulation of the drug, whereas the RAPID 2 trial evaluated the liquid form of the drug.

The 397 patients who were assigned to the 200-mg arm initially received a 400-mg loading dose of certolizumab pegol at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks. The 394 individuals in the 400-mg arm received 400 mg every 2 weeks.

The 201 placebo-treated patients followed the same schedule as the 400-mg group. If the patients did not reach an ACR 20 response by 16 weeks, they entered an open-label extension in which they received 400 mg certolizumab pegol every 2 weeks, Dr. Keystone said.

At baseline, patients averaged 52 years of age, 6 years of RA, 13 mg/week methotrexate, 1.5 treatment failures on disease-modifying antirheumatic drugs other than methotrexate, a Disease Activity Score of 7, and about 30 tender and 20 swollen joints.

On an intent-to-treat basis, similar percentages of patients who took the 200-mg and 400-mg certolizumab pegol dosages achieved an ACR 50 level of response (37% and 40%, respectively) or ACR 70 level of response (21% in each of the groups).

ACR 50 and 70 responses occurred in 8% and 3%, respectively, of patients in the placebo group.

Most patients who achieved either an ACR 50 or ACR 70 level of response did so by 16 weeks, which is earlier than has been seen with other anti-TNF agents, Dr. Keystone said.

About 80% of placebo-treated patients withdrew from the study, compared with about 25% of 400-mg patients and 30% of 200-mg patients.

Treatment-emergent adverse events, including serious events, occurred at similar rates between the groups.

There was a trend toward more nonserious and serious infections in the certolizumab pegol-treated groups.

The trial also had a primary end point of Total Modified Sharp Score at the end of 52 weeks, but Dr. Keystone did not report on it at the meeting.

Most patients who achieved an ACR 50 or ACR 70 response on the combined regimen did so by 16 weeks. DR. KEYSTONE

BARCELONA — Treatment of rheumatoid arthritis with a combination of certolizumab pegol and methotrexate improved symptoms in a significantly greater proportion of patients than methotrexate alone, according to the results of a phase III trial.

In the 52-week, multicenter, randomized, double-blind trial, about 60% of patients who received dosing regimens with either 200 mg or 400 mg of certolizumab pegol (Cimzia) and methotrexate achieved an American College of Rheumatology (ACR) 20 level of response at 24 weeks on an intent-to-treat basis, compared with only 14% of those who received placebo plus methotrexate.

An ACR 20 level of response is achieved when there is 20% improvement in the number of tender and swollen joints as well as a 20% improvement in at least three of five other parameters.

The rheumatoid arthritis patients in the current trial, which was called RAPID 1, had to have had an inadequate response to methotrexate therapy alone for at least 6 months prior to the start of the study, Dr. Edward C. Keystone reported at the annual European Congress of Rheumatology.

Certolizumab pegol is a humanized monoclonal Fab' fragment conjugated to polyethylene glycol, which prolongs the amount of time that the drug remains in the bloodstream.

It is the first anti-tumor necrosis factor-α drug to be constructed without the Fc fusion protein, which may cause adverse effects in other anti-TNF-α agents.

The drug also is produced in bacteria rather than in Chinese hamster ovary cells said Dr. Keystone, director of the Rebecca MacDonald Centre for Arthritis and Autoimmune Disease at the University of Toronto.

He has received research funds from and has been a consultant for the biopharmaceutical company Union Chimique Belge (UCB), which funded the study.

The RAPID 1 trial tested the lyophilized formulation of the drug, whereas the RAPID 2 trial evaluated the liquid form of the drug.

The 397 patients who were assigned to the 200-mg arm initially received a 400-mg loading dose of certolizumab pegol at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks. The 394 individuals in the 400-mg arm received 400 mg every 2 weeks.

The 201 placebo-treated patients followed the same schedule as the 400-mg group. If the patients did not reach an ACR 20 response by 16 weeks, they entered an open-label extension in which they received 400 mg certolizumab pegol every 2 weeks, Dr. Keystone said.

At baseline, patients averaged 52 years of age, 6 years of RA, 13 mg/week methotrexate, 1.5 treatment failures on disease-modifying antirheumatic drugs other than methotrexate, a Disease Activity Score of 7, and about 30 tender and 20 swollen joints.

On an intent-to-treat basis, similar percentages of patients who took the 200-mg and 400-mg certolizumab pegol dosages achieved an ACR 50 level of response (37% and 40%, respectively) or ACR 70 level of response (21% in each of the groups).

ACR 50 and 70 responses occurred in 8% and 3%, respectively, of patients in the placebo group.

Most patients who achieved either an ACR 50 or ACR 70 level of response did so by 16 weeks, which is earlier than has been seen with other anti-TNF agents, Dr. Keystone said.

About 80% of placebo-treated patients withdrew from the study, compared with about 25% of 400-mg patients and 30% of 200-mg patients.

Treatment-emergent adverse events, including serious events, occurred at similar rates between the groups.

There was a trend toward more nonserious and serious infections in the certolizumab pegol-treated groups.

The trial also had a primary end point of Total Modified Sharp Score at the end of 52 weeks, but Dr. Keystone did not report on it at the meeting.

Most patients who achieved an ACR 50 or ACR 70 response on the combined regimen did so by 16 weeks. DR. KEYSTONE

BARCELONA — Treatment of rheumatoid arthritis with a combination of certolizumab pegol and methotrexate improved symptoms in a significantly greater proportion of patients than methotrexate alone, according to the results of a phase III trial.

In the 52-week, multicenter, randomized, double-blind trial, about 60% of patients who received dosing regimens with either 200 mg or 400 mg of certolizumab pegol (Cimzia) and methotrexate achieved an American College of Rheumatology (ACR) 20 level of response at 24 weeks on an intent-to-treat basis, compared with only 14% of those who received placebo plus methotrexate.

An ACR 20 level of response is achieved when there is 20% improvement in the number of tender and swollen joints as well as a 20% improvement in at least three of five other parameters.

The rheumatoid arthritis patients in the current trial, which was called RAPID 1, had to have had an inadequate response to methotrexate therapy alone for at least 6 months prior to the start of the study, Dr. Edward C. Keystone reported at the annual European Congress of Rheumatology.

Certolizumab pegol is a humanized monoclonal Fab' fragment conjugated to polyethylene glycol, which prolongs the amount of time that the drug remains in the bloodstream.

It is the first anti-tumor necrosis factor-α drug to be constructed without the Fc fusion protein, which may cause adverse effects in other anti-TNF-α agents.

The drug also is produced in bacteria rather than in Chinese hamster ovary cells said Dr. Keystone, director of the Rebecca MacDonald Centre for Arthritis and Autoimmune Disease at the University of Toronto.

He has received research funds from and has been a consultant for the biopharmaceutical company Union Chimique Belge (UCB), which funded the study.

The RAPID 1 trial tested the lyophilized formulation of the drug, whereas the RAPID 2 trial evaluated the liquid form of the drug.

The 397 patients who were assigned to the 200-mg arm initially received a 400-mg loading dose of certolizumab pegol at 0, 2, and 4 weeks, followed by 200 mg every 2 weeks. The 394 individuals in the 400-mg arm received 400 mg every 2 weeks.

The 201 placebo-treated patients followed the same schedule as the 400-mg group. If the patients did not reach an ACR 20 response by 16 weeks, they entered an open-label extension in which they received 400 mg certolizumab pegol every 2 weeks, Dr. Keystone said.

At baseline, patients averaged 52 years of age, 6 years of RA, 13 mg/week methotrexate, 1.5 treatment failures on disease-modifying antirheumatic drugs other than methotrexate, a Disease Activity Score of 7, and about 30 tender and 20 swollen joints.

On an intent-to-treat basis, similar percentages of patients who took the 200-mg and 400-mg certolizumab pegol dosages achieved an ACR 50 level of response (37% and 40%, respectively) or ACR 70 level of response (21% in each of the groups).

ACR 50 and 70 responses occurred in 8% and 3%, respectively, of patients in the placebo group.

Most patients who achieved either an ACR 50 or ACR 70 level of response did so by 16 weeks, which is earlier than has been seen with other anti-TNF agents, Dr. Keystone said.

About 80% of placebo-treated patients withdrew from the study, compared with about 25% of 400-mg patients and 30% of 200-mg patients.

Treatment-emergent adverse events, including serious events, occurred at similar rates between the groups.

There was a trend toward more nonserious and serious infections in the certolizumab pegol-treated groups.

The trial also had a primary end point of Total Modified Sharp Score at the end of 52 weeks, but Dr. Keystone did not report on it at the meeting.

Most patients who achieved an ACR 50 or ACR 70 response on the combined regimen did so by 16 weeks. DR. KEYSTONE

Extremity MRI allows office-based rheumatologists to diagnose rheumatoid arthritis early in its course and then to make clinical decisions as to whether to continue a given therapy, add an additional agent to the regimen, or switch to another agent, said Dr. Norman B. Gaylis, a rheumatologist in private practice in Aventura, Fla., who performs extremity MRI in the office.

Erosions and bone marrow inflammation can be seen on MRI but not on x-ray, which makes MRI a better tool for early diagnosis. “The other way in which I think in-office MRI is extremely helpful is to see whether the treatment is working or is not working,” said Dr. Gaylis. Treatment-related changes may not be apparent on x-ray for 2 years or longer. “That's a whole lot of time to be on a drug that is… very expensive and… maybe not working,” he said.

Standard MRI (0.75 tesla or greater) has been shown to be useful in diagnosing RA and for following therapy. The great demand for MRI on the larger machines that are based in hospitals and imaging centers results in long lead times for appointments. As a result, rheumatologists don't typically take advantage of this tool. In addition, patients with active RA sometimes find it intolerably painful to hold the position necessary for imaging in large machines.

Dr. Gaylis noted that extremity MRI (0.2 tesla) is performed in the office and allows for the patient to assume a more comfortable position during imaging. In addition, slices with this type of MRI average less than 1 mm and are contiguous, which is not always true of machines with stronger magnets. This can be important because it is possible for erosions to “hide” between the slices of larger machines, he added.

Extremity MRI is twice as sensitive as radiography in detecting erosions at baseline, according to a recent study by Dr. Gaylis and his colleagues (Mod. Rheumatol. 2007;17:273-8). In the study, 31 patients underwent both baseline extremity MRI and x-ray examinations. For 108 metacarpophalangeal joints, the sensitivity of radiography was 55.8%, compared with MRI, and specificity of radiography was 95.4%. Positive predictive value was 88.9% and negative predictive value was 76.5%.

In terms of in-office set up, smaller extremity MRI machines don't have many special requirements. Extremity MRI can be set up in a standard exam room. The floors need to provide sufficient support because the magnets are heavy. “One thing that you have to be careful of is that you have an environment where there is not that much noise [which interferes with the software],” said Dr. Gaylis. It's also important to keep the room cool because of the magnet.

Although the cost varies, in-office extremity MRI equipment costs around $250,000. However, the machines are typically leased, as are many other pieces of medical equipment, said Dr. Gaylis.

Once an extremity MRI is performed, Dr. Gaylis digitally sends the image to a radiologist, who reads the image and sends back a report, usually the next day. “I like this format because it combines my knowledge of the patient with the expertise of a musculoskeletal radiologist,” he said.

MRIs are more complicated to read than are x-rays because every joint imaged with MRI yields a number of slices. “So at the end of my day, after I've seen × number of patients, for me to go and read MRIs is really not practical,” said Dr. Gaylis. In addition, musculoskeletal radiologists have a high level of expertise in reading MRIs.

“At the end of the day, I think it allows me more credibility to say that my radiologist is reading it,” he said. The rheumatologist's responsibility is to react to the MRI findings and treat the patient appropriately, Dr. Gaylis noted.

Extremity MRIs can also help improve patient compliance. Patients can see the erosions for themselves. “When they see them and they understand why we want to put them through the process of a biologic … it absolutely makes the patient more responsive to [our] therapeutic suggestions,” said Dr. Gaylis.

The MRIs can also help keep patients on the right drugs. “They get a lot more understanding when they see an MRI that reflects what's going on,” said Dr. Gaylis.

Reimbursement of extremity MRI is a tricky subject, however. Even though extremity MRI is commonplace in the orthopedic setting, there is no reimbursement code that is specific to extremity MRI. Instead, codes for the larger conventional machines are used. Getting third-party payers to foot the bill for extremity MRI can be tough, but it can be done. “We've been able to show them that they actually would save money by getting [the patient] an MRI annually. If you give someone Remicade [infliximab] and it's not working … why not find out and stop it and stop paying all that money if it's not working,” said Dr. Gaylis. He estimates that 70% of his payers are paying for extremity MRI.

The American College of Rheumatology has yet to endorse the use of the extremity MRI for RA. The organization issued a white paper 2 years ago on extremity MRI, indicating that more evidence was needed to demonstrate the validity of the technique for RA.

The International Society of Extremity MRI—which comprises rheumatologists and radiologists—currently is working on providing the ACR with enough data to review the white paper findings, according to Dr. Gaylis.

Extremity MRI. Top, carpal bone erosion; bottom, healed erosions after infliximab. Left are T1, right are STIR sequence.

The MRI images on the left (T1) and on the right (STIR) show erosions of the lunate and scaphoid bones.

A normal x-ray is shown for comparison. Photos courtesy Dr. Norman B. Gaylis/Dr. Steven Needell

Extremity MRI allows office-based rheumatologists to diagnose rheumatoid arthritis early in its course and then to make clinical decisions as to whether to continue a given therapy, add an additional agent to the regimen, or switch to another agent, said Dr. Norman B. Gaylis, a rheumatologist in private practice in Aventura, Fla., who performs extremity MRI in the office.

Erosions and bone marrow inflammation can be seen on MRI but not on x-ray, which makes MRI a better tool for early diagnosis. “The other way in which I think in-office MRI is extremely helpful is to see whether the treatment is working or is not working,” said Dr. Gaylis. Treatment-related changes may not be apparent on x-ray for 2 years or longer. “That's a whole lot of time to be on a drug that is… very expensive and… maybe not working,” he said.

Standard MRI (0.75 tesla or greater) has been shown to be useful in diagnosing RA and for following therapy. The great demand for MRI on the larger machines that are based in hospitals and imaging centers results in long lead times for appointments. As a result, rheumatologists don't typically take advantage of this tool. In addition, patients with active RA sometimes find it intolerably painful to hold the position necessary for imaging in large machines.

Dr. Gaylis noted that extremity MRI (0.2 tesla) is performed in the office and allows for the patient to assume a more comfortable position during imaging. In addition, slices with this type of MRI average less than 1 mm and are contiguous, which is not always true of machines with stronger magnets. This can be important because it is possible for erosions to “hide” between the slices of larger machines, he added.

Extremity MRI is twice as sensitive as radiography in detecting erosions at baseline, according to a recent study by Dr. Gaylis and his colleagues (Mod. Rheumatol. 2007;17:273-8). In the study, 31 patients underwent both baseline extremity MRI and x-ray examinations. For 108 metacarpophalangeal joints, the sensitivity of radiography was 55.8%, compared with MRI, and specificity of radiography was 95.4%. Positive predictive value was 88.9% and negative predictive value was 76.5%.

In terms of in-office set up, smaller extremity MRI machines don't have many special requirements. Extremity MRI can be set up in a standard exam room. The floors need to provide sufficient support because the magnets are heavy. “One thing that you have to be careful of is that you have an environment where there is not that much noise [which interferes with the software],” said Dr. Gaylis. It's also important to keep the room cool because of the magnet.

Although the cost varies, in-office extremity MRI equipment costs around $250,000. However, the machines are typically leased, as are many other pieces of medical equipment, said Dr. Gaylis.

Once an extremity MRI is performed, Dr. Gaylis digitally sends the image to a radiologist, who reads the image and sends back a report, usually the next day. “I like this format because it combines my knowledge of the patient with the expertise of a musculoskeletal radiologist,” he said.

MRIs are more complicated to read than are x-rays because every joint imaged with MRI yields a number of slices. “So at the end of my day, after I've seen × number of patients, for me to go and read MRIs is really not practical,” said Dr. Gaylis. In addition, musculoskeletal radiologists have a high level of expertise in reading MRIs.

“At the end of the day, I think it allows me more credibility to say that my radiologist is reading it,” he said. The rheumatologist's responsibility is to react to the MRI findings and treat the patient appropriately, Dr. Gaylis noted.

Extremity MRIs can also help improve patient compliance. Patients can see the erosions for themselves. “When they see them and they understand why we want to put them through the process of a biologic … it absolutely makes the patient more responsive to [our] therapeutic suggestions,” said Dr. Gaylis.

The MRIs can also help keep patients on the right drugs. “They get a lot more understanding when they see an MRI that reflects what's going on,” said Dr. Gaylis.

Reimbursement of extremity MRI is a tricky subject, however. Even though extremity MRI is commonplace in the orthopedic setting, there is no reimbursement code that is specific to extremity MRI. Instead, codes for the larger conventional machines are used. Getting third-party payers to foot the bill for extremity MRI can be tough, but it can be done. “We've been able to show them that they actually would save money by getting [the patient] an MRI annually. If you give someone Remicade [infliximab] and it's not working … why not find out and stop it and stop paying all that money if it's not working,” said Dr. Gaylis. He estimates that 70% of his payers are paying for extremity MRI.

The American College of Rheumatology has yet to endorse the use of the extremity MRI for RA. The organization issued a white paper 2 years ago on extremity MRI, indicating that more evidence was needed to demonstrate the validity of the technique for RA.

The International Society of Extremity MRI—which comprises rheumatologists and radiologists—currently is working on providing the ACR with enough data to review the white paper findings, according to Dr. Gaylis.

Extremity MRI. Top, carpal bone erosion; bottom, healed erosions after infliximab. Left are T1, right are STIR sequence.

The MRI images on the left (T1) and on the right (STIR) show erosions of the lunate and scaphoid bones.

A normal x-ray is shown for comparison. Photos courtesy Dr. Norman B. Gaylis/Dr. Steven Needell

Extremity MRI allows office-based rheumatologists to diagnose rheumatoid arthritis early in its course and then to make clinical decisions as to whether to continue a given therapy, add an additional agent to the regimen, or switch to another agent, said Dr. Norman B. Gaylis, a rheumatologist in private practice in Aventura, Fla., who performs extremity MRI in the office.

Erosions and bone marrow inflammation can be seen on MRI but not on x-ray, which makes MRI a better tool for early diagnosis. “The other way in which I think in-office MRI is extremely helpful is to see whether the treatment is working or is not working,” said Dr. Gaylis. Treatment-related changes may not be apparent on x-ray for 2 years or longer. “That's a whole lot of time to be on a drug that is… very expensive and… maybe not working,” he said.

Standard MRI (0.75 tesla or greater) has been shown to be useful in diagnosing RA and for following therapy. The great demand for MRI on the larger machines that are based in hospitals and imaging centers results in long lead times for appointments. As a result, rheumatologists don't typically take advantage of this tool. In addition, patients with active RA sometimes find it intolerably painful to hold the position necessary for imaging in large machines.

Dr. Gaylis noted that extremity MRI (0.2 tesla) is performed in the office and allows for the patient to assume a more comfortable position during imaging. In addition, slices with this type of MRI average less than 1 mm and are contiguous, which is not always true of machines with stronger magnets. This can be important because it is possible for erosions to “hide” between the slices of larger machines, he added.

Extremity MRI is twice as sensitive as radiography in detecting erosions at baseline, according to a recent study by Dr. Gaylis and his colleagues (Mod. Rheumatol. 2007;17:273-8). In the study, 31 patients underwent both baseline extremity MRI and x-ray examinations. For 108 metacarpophalangeal joints, the sensitivity of radiography was 55.8%, compared with MRI, and specificity of radiography was 95.4%. Positive predictive value was 88.9% and negative predictive value was 76.5%.

In terms of in-office set up, smaller extremity MRI machines don't have many special requirements. Extremity MRI can be set up in a standard exam room. The floors need to provide sufficient support because the magnets are heavy. “One thing that you have to be careful of is that you have an environment where there is not that much noise [which interferes with the software],” said Dr. Gaylis. It's also important to keep the room cool because of the magnet.

Although the cost varies, in-office extremity MRI equipment costs around $250,000. However, the machines are typically leased, as are many other pieces of medical equipment, said Dr. Gaylis.

Once an extremity MRI is performed, Dr. Gaylis digitally sends the image to a radiologist, who reads the image and sends back a report, usually the next day. “I like this format because it combines my knowledge of the patient with the expertise of a musculoskeletal radiologist,” he said.

MRIs are more complicated to read than are x-rays because every joint imaged with MRI yields a number of slices. “So at the end of my day, after I've seen × number of patients, for me to go and read MRIs is really not practical,” said Dr. Gaylis. In addition, musculoskeletal radiologists have a high level of expertise in reading MRIs.

“At the end of the day, I think it allows me more credibility to say that my radiologist is reading it,” he said. The rheumatologist's responsibility is to react to the MRI findings and treat the patient appropriately, Dr. Gaylis noted.

Extremity MRIs can also help improve patient compliance. Patients can see the erosions for themselves. “When they see them and they understand why we want to put them through the process of a biologic … it absolutely makes the patient more responsive to [our] therapeutic suggestions,” said Dr. Gaylis.

The MRIs can also help keep patients on the right drugs. “They get a lot more understanding when they see an MRI that reflects what's going on,” said Dr. Gaylis.

Reimbursement of extremity MRI is a tricky subject, however. Even though extremity MRI is commonplace in the orthopedic setting, there is no reimbursement code that is specific to extremity MRI. Instead, codes for the larger conventional machines are used. Getting third-party payers to foot the bill for extremity MRI can be tough, but it can be done. “We've been able to show them that they actually would save money by getting [the patient] an MRI annually. If you give someone Remicade [infliximab] and it's not working … why not find out and stop it and stop paying all that money if it's not working,” said Dr. Gaylis. He estimates that 70% of his payers are paying for extremity MRI.

The American College of Rheumatology has yet to endorse the use of the extremity MRI for RA. The organization issued a white paper 2 years ago on extremity MRI, indicating that more evidence was needed to demonstrate the validity of the technique for RA.

The International Society of Extremity MRI—which comprises rheumatologists and radiologists—currently is working on providing the ACR with enough data to review the white paper findings, according to Dr. Gaylis.

Extremity MRI. Top, carpal bone erosion; bottom, healed erosions after infliximab. Left are T1, right are STIR sequence.

The MRI images on the left (T1) and on the right (STIR) show erosions of the lunate and scaphoid bones.

A normal x-ray is shown for comparison. Photos courtesy Dr. Norman B. Gaylis/Dr. Steven Needell

BARCELONA — In a multicenter double-blind study, treatment with the interleukin-6 signaling blocker tocilizumab not only significantly reduced disease activity among patients with rheumatoid arthritis but also improved physical function, fatigue, and quality of life.

A total of 622 patients with moderate to severe rheumatoid arthritis (RA) were randomized to receive intravenous tocilizumab in doses of 4 mg/kg or 8 mg/kg every 4 weeks or placebo. They also received background methotrexate in doses of 10–25 mg/week and corticosteroids in doses of 10 mg/day or less, according to Dr. Rieke H.E. Alten of the Schlosspark Klinik, Berlin.

Patients' mean age was 51 years, and more than half were women. Mean disease duration was 7.5 years, and study participants had taken a mean of 1.5 disease-modifying antirheumatic drugs before undertaking the experimental regimen.

All patients had swollen joint counts of six or more and tender joint counts of at least eight.

By week 24, a significantly greater proportion of patients treated with tocilizumab achieved an American College of Rheumatology (ACR) 20 response than did those who received placebo. Among patients in the low-dose tocilizumab group, 13.5% achieved this level of response, as did 27.5% of those in the high-dose group. Among those receiving placebo, 0.8% reached an ACR20 level of response, Dr. Alten reported in a poster session at the annual European Congress of Rheumatology.

Tocilizumab treatment also resulted in a marked increase in the proportion of patients who achieved moderate or good response according to the criteria of the European League Against Rheumatism. A total of 61.9% and 79.5% of patients in the low- and high-dose groups, respectively, had moderate or good responses.

On the Health Assessment Questionnaire Disability Index (HAQ-DI), clinically relevant improvements were seen in patients in both tocilizumab groups, starting at week 4, and with greater mean reductions than the protocol-defined minimally clinically difference of −0.25.

Among patients in the tocilizumab 4 mg/kg and 8 mg/kg groups, 64.8% and 63.1%, respectively, had a 20% or greater improvement in HAQ-DI, compared with 47.5% of the placebo patients.

All treatment groups showed improvements in the physical and mental components of the Short Form-36 Health Survey.

Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale scores also improved in all treatment groups, but greater mean changes were consistently observed for patients in the tocilizumab groups, Dr. Alten wrote.

Moreover, the FACIT fatigue score increased by a clinically meaningful four points or more from baseline by week 4 in both tocilizumab groups.

RA is associated with functional disability, limitation of daily activities, and decreased quality of life. Fatigue is a particular problem, with more than 40% of patients reporting clinically important levels of fatigue, Dr. Alten noted.

The rationale for targeting IL-6 in RA lies in observations that this cytokine appears to play a role in the damage to periarticular bone and cartilage. It also activates T cells, B cells, and macrophages and is a central mediator of the hepatic acute phase response (Lancet 2007; [doi:10.1016/S0140-6736(07)60784-3]).

The study was sponsored by Hoffmann-La Roche Inc.

ELSEVIER GLOBAL MEDICAL NEWS

BARCELONA — In a multicenter double-blind study, treatment with the interleukin-6 signaling blocker tocilizumab not only significantly reduced disease activity among patients with rheumatoid arthritis but also improved physical function, fatigue, and quality of life.

A total of 622 patients with moderate to severe rheumatoid arthritis (RA) were randomized to receive intravenous tocilizumab in doses of 4 mg/kg or 8 mg/kg every 4 weeks or placebo. They also received background methotrexate in doses of 10–25 mg/week and corticosteroids in doses of 10 mg/day or less, according to Dr. Rieke H.E. Alten of the Schlosspark Klinik, Berlin.

Patients' mean age was 51 years, and more than half were women. Mean disease duration was 7.5 years, and study participants had taken a mean of 1.5 disease-modifying antirheumatic drugs before undertaking the experimental regimen.

All patients had swollen joint counts of six or more and tender joint counts of at least eight.

By week 24, a significantly greater proportion of patients treated with tocilizumab achieved an American College of Rheumatology (ACR) 20 response than did those who received placebo. Among patients in the low-dose tocilizumab group, 13.5% achieved this level of response, as did 27.5% of those in the high-dose group. Among those receiving placebo, 0.8% reached an ACR20 level of response, Dr. Alten reported in a poster session at the annual European Congress of Rheumatology.

Tocilizumab treatment also resulted in a marked increase in the proportion of patients who achieved moderate or good response according to the criteria of the European League Against Rheumatism. A total of 61.9% and 79.5% of patients in the low- and high-dose groups, respectively, had moderate or good responses.

On the Health Assessment Questionnaire Disability Index (HAQ-DI), clinically relevant improvements were seen in patients in both tocilizumab groups, starting at week 4, and with greater mean reductions than the protocol-defined minimally clinically difference of −0.25.

Among patients in the tocilizumab 4 mg/kg and 8 mg/kg groups, 64.8% and 63.1%, respectively, had a 20% or greater improvement in HAQ-DI, compared with 47.5% of the placebo patients.

All treatment groups showed improvements in the physical and mental components of the Short Form-36 Health Survey.

Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale scores also improved in all treatment groups, but greater mean changes were consistently observed for patients in the tocilizumab groups, Dr. Alten wrote.

Moreover, the FACIT fatigue score increased by a clinically meaningful four points or more from baseline by week 4 in both tocilizumab groups.

RA is associated with functional disability, limitation of daily activities, and decreased quality of life. Fatigue is a particular problem, with more than 40% of patients reporting clinically important levels of fatigue, Dr. Alten noted.

The rationale for targeting IL-6 in RA lies in observations that this cytokine appears to play a role in the damage to periarticular bone and cartilage. It also activates T cells, B cells, and macrophages and is a central mediator of the hepatic acute phase response (Lancet 2007; [doi:10.1016/S0140-6736(07)60784-3]).

The study was sponsored by Hoffmann-La Roche Inc.

ELSEVIER GLOBAL MEDICAL NEWS

BARCELONA — In a multicenter double-blind study, treatment with the interleukin-6 signaling blocker tocilizumab not only significantly reduced disease activity among patients with rheumatoid arthritis but also improved physical function, fatigue, and quality of life.

A total of 622 patients with moderate to severe rheumatoid arthritis (RA) were randomized to receive intravenous tocilizumab in doses of 4 mg/kg or 8 mg/kg every 4 weeks or placebo. They also received background methotrexate in doses of 10–25 mg/week and corticosteroids in doses of 10 mg/day or less, according to Dr. Rieke H.E. Alten of the Schlosspark Klinik, Berlin.

Patients' mean age was 51 years, and more than half were women. Mean disease duration was 7.5 years, and study participants had taken a mean of 1.5 disease-modifying antirheumatic drugs before undertaking the experimental regimen.

All patients had swollen joint counts of six or more and tender joint counts of at least eight.

By week 24, a significantly greater proportion of patients treated with tocilizumab achieved an American College of Rheumatology (ACR) 20 response than did those who received placebo. Among patients in the low-dose tocilizumab group, 13.5% achieved this level of response, as did 27.5% of those in the high-dose group. Among those receiving placebo, 0.8% reached an ACR20 level of response, Dr. Alten reported in a poster session at the annual European Congress of Rheumatology.

Tocilizumab treatment also resulted in a marked increase in the proportion of patients who achieved moderate or good response according to the criteria of the European League Against Rheumatism. A total of 61.9% and 79.5% of patients in the low- and high-dose groups, respectively, had moderate or good responses.

On the Health Assessment Questionnaire Disability Index (HAQ-DI), clinically relevant improvements were seen in patients in both tocilizumab groups, starting at week 4, and with greater mean reductions than the protocol-defined minimally clinically difference of −0.25.

Among patients in the tocilizumab 4 mg/kg and 8 mg/kg groups, 64.8% and 63.1%, respectively, had a 20% or greater improvement in HAQ-DI, compared with 47.5% of the placebo patients.

All treatment groups showed improvements in the physical and mental components of the Short Form-36 Health Survey.

Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Scale scores also improved in all treatment groups, but greater mean changes were consistently observed for patients in the tocilizumab groups, Dr. Alten wrote.

Moreover, the FACIT fatigue score increased by a clinically meaningful four points or more from baseline by week 4 in both tocilizumab groups.

RA is associated with functional disability, limitation of daily activities, and decreased quality of life. Fatigue is a particular problem, with more than 40% of patients reporting clinically important levels of fatigue, Dr. Alten noted.

The rationale for targeting IL-6 in RA lies in observations that this cytokine appears to play a role in the damage to periarticular bone and cartilage. It also activates T cells, B cells, and macrophages and is a central mediator of the hepatic acute phase response (Lancet 2007; [doi:10.1016/S0140-6736(07)60784-3]).

The study was sponsored by Hoffmann-La Roche Inc.

ELSEVIER GLOBAL MEDICAL NEWS

BOSTON— To differentiate definitively between acute gout and pseudogout, look at the crystals.

On UV light microscopy, fluid aspirated from the inflamed joint of a patient with pseudogout will be teeming with rhomboid-shaped calcium pyrophosphate dihydrate (CPPD) crystals, which are morphologically different from the needle-shaped monosodium urate (MSU) crystals implicated in the pain and swelling of acute gout, Dr. Dwight R. Robinson said at a meeting on rheumatology sponsored by Harvard Medical School. “Calcium pyrophosphate dihydrate crystals are less well formed and show more variation in size and shape than monosodium urate crystals. In that way, they are a little more difficult to identify.”

Like MSU crystals in the joints of gout patients, the deposition of CPPD crystals in pseudogout causes acute pain and swelling in one or multiple joints. The acute attacks can last anywhere from 1 day to 4 weeks and sometimes are accompanied by fever, leukocytosis, and elevated acute-phase reactants said Dr. Robinson, a rheumatologist and professor of medicine at Harvard Medical School, Boston. Because the latter signs also may be indicative of septic arthritis, sepsis first must be excluded by gram stain and culture of synovial fluid.

In general, CPPD crystals have a predilection for depositing in articular and fibrocartilage, said Dr. Robinson. In pseudogout, this process commonly involves the knee or wrist joint but also may involve the first metatarsophalangeal joint, as occurs in gout, or almost any other joint, he said. Radiographically, the diagnosis of pseudogout often can be confirmed by evidence of chondrocalcinosis in the affected joint space.

In addition to mimicking the clinical patterns of gout, the symptoms of CPPD joint disease may overlap with other inflammatory conditions. “The disease may present as pseudorheumatoid arthritis, pseudo-osteoarthritis with or without pseudogout, or pseudoneuropathic arthritis,” said Dr. Robinson. “In many patients, the condition is actually asymptomatic.”

CPPD disease develops idiopathically in individuals older than age 50. In younger patients, “it's more likely to be a complication of osteoarthritis, a late consequence of joint trauma or knee meniscectomy, or related to an underlying metabolic disease, such as hyperparathyroidism, dialysis-dependent renal failure, hemochromatosis, and hypomagnesemia,” said Dr. Robinson, noting that there also may be a familial component.

Although the exact mechanism for the development of CPPD deposition disease is uncertain, an overactivity of enzymes that break down nucleoside triphosphates has been implicated, as have genetic defects, specifically mutations in the human homologue of the murine ANK gene. “Several mutations in the [human homologue] may be responsible for human disease, including CPPD arthropath,” said Dr. Robinson.

There currently are no proven prophylactic therapies for pseudogout, but acute attacks can be treated effectively with, primarily, nonsteroidal anti-inflammatory drugs, said Dr. Robinson. Given the risks of gastrointestinal and renal toxicities associated with NSAIDs, particularly in elderly patients, intra-articular corticosteroid injection into the affected joint is a reasonable treatment option, he said, as is a short course of systemic corticosteroids for polyarticular pseudogout attacks. Oral or intravenous colchicine should be considered only as a treatment of last resort because of the associated risks of gastrointestinal and other toxicities.

BOSTON— To differentiate definitively between acute gout and pseudogout, look at the crystals.

On UV light microscopy, fluid aspirated from the inflamed joint of a patient with pseudogout will be teeming with rhomboid-shaped calcium pyrophosphate dihydrate (CPPD) crystals, which are morphologically different from the needle-shaped monosodium urate (MSU) crystals implicated in the pain and swelling of acute gout, Dr. Dwight R. Robinson said at a meeting on rheumatology sponsored by Harvard Medical School. “Calcium pyrophosphate dihydrate crystals are less well formed and show more variation in size and shape than monosodium urate crystals. In that way, they are a little more difficult to identify.”

Like MSU crystals in the joints of gout patients, the deposition of CPPD crystals in pseudogout causes acute pain and swelling in one or multiple joints. The acute attacks can last anywhere from 1 day to 4 weeks and sometimes are accompanied by fever, leukocytosis, and elevated acute-phase reactants said Dr. Robinson, a rheumatologist and professor of medicine at Harvard Medical School, Boston. Because the latter signs also may be indicative of septic arthritis, sepsis first must be excluded by gram stain and culture of synovial fluid.

In general, CPPD crystals have a predilection for depositing in articular and fibrocartilage, said Dr. Robinson. In pseudogout, this process commonly involves the knee or wrist joint but also may involve the first metatarsophalangeal joint, as occurs in gout, or almost any other joint, he said. Radiographically, the diagnosis of pseudogout often can be confirmed by evidence of chondrocalcinosis in the affected joint space.

In addition to mimicking the clinical patterns of gout, the symptoms of CPPD joint disease may overlap with other inflammatory conditions. “The disease may present as pseudorheumatoid arthritis, pseudo-osteoarthritis with or without pseudogout, or pseudoneuropathic arthritis,” said Dr. Robinson. “In many patients, the condition is actually asymptomatic.”

CPPD disease develops idiopathically in individuals older than age 50. In younger patients, “it's more likely to be a complication of osteoarthritis, a late consequence of joint trauma or knee meniscectomy, or related to an underlying metabolic disease, such as hyperparathyroidism, dialysis-dependent renal failure, hemochromatosis, and hypomagnesemia,” said Dr. Robinson, noting that there also may be a familial component.

Although the exact mechanism for the development of CPPD deposition disease is uncertain, an overactivity of enzymes that break down nucleoside triphosphates has been implicated, as have genetic defects, specifically mutations in the human homologue of the murine ANK gene. “Several mutations in the [human homologue] may be responsible for human disease, including CPPD arthropath,” said Dr. Robinson.

There currently are no proven prophylactic therapies for pseudogout, but acute attacks can be treated effectively with, primarily, nonsteroidal anti-inflammatory drugs, said Dr. Robinson. Given the risks of gastrointestinal and renal toxicities associated with NSAIDs, particularly in elderly patients, intra-articular corticosteroid injection into the affected joint is a reasonable treatment option, he said, as is a short course of systemic corticosteroids for polyarticular pseudogout attacks. Oral or intravenous colchicine should be considered only as a treatment of last resort because of the associated risks of gastrointestinal and other toxicities.

BOSTON— To differentiate definitively between acute gout and pseudogout, look at the crystals.

On UV light microscopy, fluid aspirated from the inflamed joint of a patient with pseudogout will be teeming with rhomboid-shaped calcium pyrophosphate dihydrate (CPPD) crystals, which are morphologically different from the needle-shaped monosodium urate (MSU) crystals implicated in the pain and swelling of acute gout, Dr. Dwight R. Robinson said at a meeting on rheumatology sponsored by Harvard Medical School. “Calcium pyrophosphate dihydrate crystals are less well formed and show more variation in size and shape than monosodium urate crystals. In that way, they are a little more difficult to identify.”

Like MSU crystals in the joints of gout patients, the deposition of CPPD crystals in pseudogout causes acute pain and swelling in one or multiple joints. The acute attacks can last anywhere from 1 day to 4 weeks and sometimes are accompanied by fever, leukocytosis, and elevated acute-phase reactants said Dr. Robinson, a rheumatologist and professor of medicine at Harvard Medical School, Boston. Because the latter signs also may be indicative of septic arthritis, sepsis first must be excluded by gram stain and culture of synovial fluid.

In general, CPPD crystals have a predilection for depositing in articular and fibrocartilage, said Dr. Robinson. In pseudogout, this process commonly involves the knee or wrist joint but also may involve the first metatarsophalangeal joint, as occurs in gout, or almost any other joint, he said. Radiographically, the diagnosis of pseudogout often can be confirmed by evidence of chondrocalcinosis in the affected joint space.

In addition to mimicking the clinical patterns of gout, the symptoms of CPPD joint disease may overlap with other inflammatory conditions. “The disease may present as pseudorheumatoid arthritis, pseudo-osteoarthritis with or without pseudogout, or pseudoneuropathic arthritis,” said Dr. Robinson. “In many patients, the condition is actually asymptomatic.”

CPPD disease develops idiopathically in individuals older than age 50. In younger patients, “it's more likely to be a complication of osteoarthritis, a late consequence of joint trauma or knee meniscectomy, or related to an underlying metabolic disease, such as hyperparathyroidism, dialysis-dependent renal failure, hemochromatosis, and hypomagnesemia,” said Dr. Robinson, noting that there also may be a familial component.

Although the exact mechanism for the development of CPPD deposition disease is uncertain, an overactivity of enzymes that break down nucleoside triphosphates has been implicated, as have genetic defects, specifically mutations in the human homologue of the murine ANK gene. “Several mutations in the [human homologue] may be responsible for human disease, including CPPD arthropath,” said Dr. Robinson.

There currently are no proven prophylactic therapies for pseudogout, but acute attacks can be treated effectively with, primarily, nonsteroidal anti-inflammatory drugs, said Dr. Robinson. Given the risks of gastrointestinal and renal toxicities associated with NSAIDs, particularly in elderly patients, intra-articular corticosteroid injection into the affected joint is a reasonable treatment option, he said, as is a short course of systemic corticosteroids for polyarticular pseudogout attacks. Oral or intravenous colchicine should be considered only as a treatment of last resort because of the associated risks of gastrointestinal and other toxicities.

The fibromyalgia guidelines issued by EULAR represent a work in progress on a field “that is very much in evolution,” Dr. Philip J. Mease said in an interview.

The recommendations were formulated by a European working group that included specialists from various fields including rheumatology, pain medicine, and neurology, who reviewed all the available trials through 2005.

“They have done a good job with a difficult challenge, because the trials are so different, both in terms of the outcome measures used and the treatment approaches tried,” said Dr. Mease, a rheumatologist at the Univeristy of Washington, Seattle, and chief of clinical research at the Swedish Hospital Medical Center, Seattle.

“Moreover, they used a balanced way of looking at both pharmacologic and nonpharmacologic approaches, to give the managing physician a choice of therapeutic approaches,” he said.

Among the general recommendations were the concepts that fibromyalgia requires a comprehensive assessment of pain, function, and psychosocial context. Treatment should be multidisciplinary, combining various modalities tailored to pain intensity, function, and associated features such as depression and fatigue. While recommendations were evidence-based where possible, these general recommendations regarding the heterogeneity of fibromyalgia and the need for multidisciplinary treatment were based on expert opinion.

Among the recommendations for nonpharmacologic measures were the use of heated pool treatment, with or without exercise. This modality was found to be effective in improving pain and function in several “fairly high-quality” trials, according to the investigators.

They reported that tailored exercise programs including aerobic exercise and strength training can be useful for some patients, and noted that the evidence in the literature for this recommendation is poor, with many open trials and inadequate blinding. However, given the safety and overall health benefits associated with exercise, they felt this should be included in the recommendations.

They also suggested cognitive-behavioral therapy may be beneficial for some patients. This recommendation was based on expert opinion, but the only two studies identified that evaluated this approach were of poor quality. However, “This is another area in which the poor quality of trials has masked what experts believe to be a realistic reflection of possible benefits,” and cited potential improvements in pain and function (Ann. Rheum. Dis. July 20, 2007 [Epub doi:10.1136/ard.2007.071522]).

Other therapies such as relaxation, rehabilitation, physiotherapy, and psychological support also may be used, depending on individual needs. Some experimental evidence exists for the use of physiotherapy and connective tissue massage, but the recommendation for other such therapies, again, was based on expert opinion.

With regard to pharmacologic treatments, the working group recommended tramadol for the management of pain, based on two randomized controlled trials. They also favored the use of acetaminophen and other weak opioids.

However, they advised against the use of corticosteroids and strong opioids, because of their potential for significant long-term side effects and a scarcity of clinical trial data.

Antidepressants should be considered, the recommendations state, because of their ability to reduce pain and often to improve function. Amitriptyline, for example, was found to be beneficial in four of five trials that assessed pain according to a visual analogue scale (VAS).

The amitriptyline data exemplify a difficulty the investigators faced in their analysis when there were multiple trials evaluating the same drug, in that they averaged the effect sizes in these trials. With some trials being of high quality and others not, this may have skewed in an adverse way the effect size for amitriptyline, Dr. Mease observed.

Other antidepressants that have shown benefits in varying numbers and sizes of trials were fluoxetine, duloxetine, milnacipran, moclobemide, and pirlindole.

Another limitation acknowledged by the investigators was that for outcome measures they primarily relied on changes in pain assessed by VAS, and function as measured by the Fibromyalgia Impact Questionnaire (FIQ). They did not include the Short Form Health Survey (SF-36) or a patient global response, and today the outcome triad being used by the Food and Drug Administration to evaluate drugs for fibromyalgia includes a pain measure, some measure of function, and a patient global measure, said Dr. Mease, who chairs the international initiative on improving outcome measures in rheumatology known as OMERACT.

Finally, the investigators stated tropisetron, pramipexole, and pregabalin reduce pain and should be considered for the treatment of fibromyalgia. This recommendation illustrates a further difficulty faced by the EULAR group. “Both pregabalin and pramipexole are recommended, but if you look at the specific trials they are vastly different,” Dr. Mease said. Pregabalin was evaluated in a multicenter, 500-plus patient trial that was very well controlled and excluded all other drugs that might influence fibromyalgia. In contrast, the pramipexole trial took place in a single center, with fewer patients and, importantly, permitted the use of background drugs including opioids, he said.

“This was a Herculean effort that was timely and appropriate, given the rising interest in fibromyalgia as a common condition that needs more attention,” he said.

Another fibromyalgia expert, Dr. Robert M. Bennett of Oregon Health and Science University, Portland, offered a caution about pharmacotherapy in fibromyalgia. For instance, no mention is made of sleep medications or the adverse interactions of medications. “Tramadol has a dual action, as a weak opioid and a serotonin and norepinephrine reuptake inhibitor, and may interact with antidepressants, especially the monoamine oxidase inhibitors moclobemide and pirlindole, to induce a serotonin syndrome,” Dr. Bennett explained in an interview.

The guidelines will be updated every 5 years, with the hope that good quality clinical trials will continue to add to the available evidence, wrote the investigators.

'Both pregabalin and pramipexole are recommended, but if you look at the specific trials they are vastly different.' DR. MEASE

The fibromyalgia guidelines issued by EULAR represent a work in progress on a field “that is very much in evolution,” Dr. Philip J. Mease said in an interview.

The recommendations were formulated by a European working group that included specialists from various fields including rheumatology, pain medicine, and neurology, who reviewed all the available trials through 2005.

“They have done a good job with a difficult challenge, because the trials are so different, both in terms of the outcome measures used and the treatment approaches tried,” said Dr. Mease, a rheumatologist at the Univeristy of Washington, Seattle, and chief of clinical research at the Swedish Hospital Medical Center, Seattle.

“Moreover, they used a balanced way of looking at both pharmacologic and nonpharmacologic approaches, to give the managing physician a choice of therapeutic approaches,” he said.

Among the general recommendations were the concepts that fibromyalgia requires a comprehensive assessment of pain, function, and psychosocial context. Treatment should be multidisciplinary, combining various modalities tailored to pain intensity, function, and associated features such as depression and fatigue. While recommendations were evidence-based where possible, these general recommendations regarding the heterogeneity of fibromyalgia and the need for multidisciplinary treatment were based on expert opinion.

Among the recommendations for nonpharmacologic measures were the use of heated pool treatment, with or without exercise. This modality was found to be effective in improving pain and function in several “fairly high-quality” trials, according to the investigators.

They reported that tailored exercise programs including aerobic exercise and strength training can be useful for some patients, and noted that the evidence in the literature for this recommendation is poor, with many open trials and inadequate blinding. However, given the safety and overall health benefits associated with exercise, they felt this should be included in the recommendations.

They also suggested cognitive-behavioral therapy may be beneficial for some patients. This recommendation was based on expert opinion, but the only two studies identified that evaluated this approach were of poor quality. However, “This is another area in which the poor quality of trials has masked what experts believe to be a realistic reflection of possible benefits,” and cited potential improvements in pain and function (Ann. Rheum. Dis. July 20, 2007 [Epub doi:10.1136/ard.2007.071522]).

Other therapies such as relaxation, rehabilitation, physiotherapy, and psychological support also may be used, depending on individual needs. Some experimental evidence exists for the use of physiotherapy and connective tissue massage, but the recommendation for other such therapies, again, was based on expert opinion.

With regard to pharmacologic treatments, the working group recommended tramadol for the management of pain, based on two randomized controlled trials. They also favored the use of acetaminophen and other weak opioids.

However, they advised against the use of corticosteroids and strong opioids, because of their potential for significant long-term side effects and a scarcity of clinical trial data.

Antidepressants should be considered, the recommendations state, because of their ability to reduce pain and often to improve function. Amitriptyline, for example, was found to be beneficial in four of five trials that assessed pain according to a visual analogue scale (VAS).

The amitriptyline data exemplify a difficulty the investigators faced in their analysis when there were multiple trials evaluating the same drug, in that they averaged the effect sizes in these trials. With some trials being of high quality and others not, this may have skewed in an adverse way the effect size for amitriptyline, Dr. Mease observed.

Other antidepressants that have shown benefits in varying numbers and sizes of trials were fluoxetine, duloxetine, milnacipran, moclobemide, and pirlindole.

Another limitation acknowledged by the investigators was that for outcome measures they primarily relied on changes in pain assessed by VAS, and function as measured by the Fibromyalgia Impact Questionnaire (FIQ). They did not include the Short Form Health Survey (SF-36) or a patient global response, and today the outcome triad being used by the Food and Drug Administration to evaluate drugs for fibromyalgia includes a pain measure, some measure of function, and a patient global measure, said Dr. Mease, who chairs the international initiative on improving outcome measures in rheumatology known as OMERACT.

Finally, the investigators stated tropisetron, pramipexole, and pregabalin reduce pain and should be considered for the treatment of fibromyalgia. This recommendation illustrates a further difficulty faced by the EULAR group. “Both pregabalin and pramipexole are recommended, but if you look at the specific trials they are vastly different,” Dr. Mease said. Pregabalin was evaluated in a multicenter, 500-plus patient trial that was very well controlled and excluded all other drugs that might influence fibromyalgia. In contrast, the pramipexole trial took place in a single center, with fewer patients and, importantly, permitted the use of background drugs including opioids, he said.

“This was a Herculean effort that was timely and appropriate, given the rising interest in fibromyalgia as a common condition that needs more attention,” he said.

Another fibromyalgia expert, Dr. Robert M. Bennett of Oregon Health and Science University, Portland, offered a caution about pharmacotherapy in fibromyalgia. For instance, no mention is made of sleep medications or the adverse interactions of medications. “Tramadol has a dual action, as a weak opioid and a serotonin and norepinephrine reuptake inhibitor, and may interact with antidepressants, especially the monoamine oxidase inhibitors moclobemide and pirlindole, to induce a serotonin syndrome,” Dr. Bennett explained in an interview.

The guidelines will be updated every 5 years, with the hope that good quality clinical trials will continue to add to the available evidence, wrote the investigators.

'Both pregabalin and pramipexole are recommended, but if you look at the specific trials they are vastly different.' DR. MEASE

The fibromyalgia guidelines issued by EULAR represent a work in progress on a field “that is very much in evolution,” Dr. Philip J. Mease said in an interview.

The recommendations were formulated by a European working group that included specialists from various fields including rheumatology, pain medicine, and neurology, who reviewed all the available trials through 2005.

“They have done a good job with a difficult challenge, because the trials are so different, both in terms of the outcome measures used and the treatment approaches tried,” said Dr. Mease, a rheumatologist at the Univeristy of Washington, Seattle, and chief of clinical research at the Swedish Hospital Medical Center, Seattle.

“Moreover, they used a balanced way of looking at both pharmacologic and nonpharmacologic approaches, to give the managing physician a choice of therapeutic approaches,” he said.

Among the general recommendations were the concepts that fibromyalgia requires a comprehensive assessment of pain, function, and psychosocial context. Treatment should be multidisciplinary, combining various modalities tailored to pain intensity, function, and associated features such as depression and fatigue. While recommendations were evidence-based where possible, these general recommendations regarding the heterogeneity of fibromyalgia and the need for multidisciplinary treatment were based on expert opinion.

Among the recommendations for nonpharmacologic measures were the use of heated pool treatment, with or without exercise. This modality was found to be effective in improving pain and function in several “fairly high-quality” trials, according to the investigators.

They reported that tailored exercise programs including aerobic exercise and strength training can be useful for some patients, and noted that the evidence in the literature for this recommendation is poor, with many open trials and inadequate blinding. However, given the safety and overall health benefits associated with exercise, they felt this should be included in the recommendations.

They also suggested cognitive-behavioral therapy may be beneficial for some patients. This recommendation was based on expert opinion, but the only two studies identified that evaluated this approach were of poor quality. However, “This is another area in which the poor quality of trials has masked what experts believe to be a realistic reflection of possible benefits,” and cited potential improvements in pain and function (Ann. Rheum. Dis. July 20, 2007 [Epub doi:10.1136/ard.2007.071522]).

Other therapies such as relaxation, rehabilitation, physiotherapy, and psychological support also may be used, depending on individual needs. Some experimental evidence exists for the use of physiotherapy and connective tissue massage, but the recommendation for other such therapies, again, was based on expert opinion.

With regard to pharmacologic treatments, the working group recommended tramadol for the management of pain, based on two randomized controlled trials. They also favored the use of acetaminophen and other weak opioids.

However, they advised against the use of corticosteroids and strong opioids, because of their potential for significant long-term side effects and a scarcity of clinical trial data.

Antidepressants should be considered, the recommendations state, because of their ability to reduce pain and often to improve function. Amitriptyline, for example, was found to be beneficial in four of five trials that assessed pain according to a visual analogue scale (VAS).

The amitriptyline data exemplify a difficulty the investigators faced in their analysis when there were multiple trials evaluating the same drug, in that they averaged the effect sizes in these trials. With some trials being of high quality and others not, this may have skewed in an adverse way the effect size for amitriptyline, Dr. Mease observed.

Other antidepressants that have shown benefits in varying numbers and sizes of trials were fluoxetine, duloxetine, milnacipran, moclobemide, and pirlindole.

Another limitation acknowledged by the investigators was that for outcome measures they primarily relied on changes in pain assessed by VAS, and function as measured by the Fibromyalgia Impact Questionnaire (FIQ). They did not include the Short Form Health Survey (SF-36) or a patient global response, and today the outcome triad being used by the Food and Drug Administration to evaluate drugs for fibromyalgia includes a pain measure, some measure of function, and a patient global measure, said Dr. Mease, who chairs the international initiative on improving outcome measures in rheumatology known as OMERACT.

Finally, the investigators stated tropisetron, pramipexole, and pregabalin reduce pain and should be considered for the treatment of fibromyalgia. This recommendation illustrates a further difficulty faced by the EULAR group. “Both pregabalin and pramipexole are recommended, but if you look at the specific trials they are vastly different,” Dr. Mease said. Pregabalin was evaluated in a multicenter, 500-plus patient trial that was very well controlled and excluded all other drugs that might influence fibromyalgia. In contrast, the pramipexole trial took place in a single center, with fewer patients and, importantly, permitted the use of background drugs including opioids, he said.

“This was a Herculean effort that was timely and appropriate, given the rising interest in fibromyalgia as a common condition that needs more attention,” he said.

Another fibromyalgia expert, Dr. Robert M. Bennett of Oregon Health and Science University, Portland, offered a caution about pharmacotherapy in fibromyalgia. For instance, no mention is made of sleep medications or the adverse interactions of medications. “Tramadol has a dual action, as a weak opioid and a serotonin and norepinephrine reuptake inhibitor, and may interact with antidepressants, especially the monoamine oxidase inhibitors moclobemide and pirlindole, to induce a serotonin syndrome,” Dr. Bennett explained in an interview.

The guidelines will be updated every 5 years, with the hope that good quality clinical trials will continue to add to the available evidence, wrote the investigators.

'Both pregabalin and pramipexole are recommended, but if you look at the specific trials they are vastly different.' DR. MEASE

BARCELONA, SPAIN — Rheumatoid arthritis patients in remission while taking the standard dose of etanercept may be able to switch to a lower dosing regimen and still maintain remission, Dr. Leonardo Punzi reported at the annual European Congress of Rheumatology.

He presented the results of a single-center trial. He looked at 105 adult rheumatoid arthritis (RA) patients who had maintained a Disease Activity Score of less than 1.6 for at least 6 months (defined as remission) on the standard dose of etanercept (Enbrel) in combination with a methotrexate regimen (7.5–10 mg/week). The patients were randomized to receive either a continuation of the standard dose of etanercept (25 mg twice per week) or a lower dose of the drug (25 mg once per week) for 24 weeks. The investigators excluded patients who had received other tumor necrosis factor-α antagonists prior to the trial. Methotrexate and other drugs were kept at the same dosages as before the trial.

At the end of the trial, the percentage of patients who maintained remission on the Disease Activity Score was similar in the lower-dose (73%, 38 of 52) and standard-dose groups (89%, 47 of 53), said Dr. Punzi of the rheumatology unit in the department of clinical and experimental medicine at the University of Padua (Italy).

All of the 14 patients in the lower-dose group who did not maintain remission and withdrew from the trial because of a lack of efficacy returned to the standard dose; 9 (64%) of them again achieved remission, whereas the other 5 switched to another anti-TNF-α drug.

Scores on the Health Assessment Questionnaire also did not differ significantly between the groups at 8, 16, and 24 weeks. Adverse events, including serious infections, occurred at similar rates in each group.

BARCELONA, SPAIN — Rheumatoid arthritis patients in remission while taking the standard dose of etanercept may be able to switch to a lower dosing regimen and still maintain remission, Dr. Leonardo Punzi reported at the annual European Congress of Rheumatology.

He presented the results of a single-center trial. He looked at 105 adult rheumatoid arthritis (RA) patients who had maintained a Disease Activity Score of less than 1.6 for at least 6 months (defined as remission) on the standard dose of etanercept (Enbrel) in combination with a methotrexate regimen (7.5–10 mg/week). The patients were randomized to receive either a continuation of the standard dose of etanercept (25 mg twice per week) or a lower dose of the drug (25 mg once per week) for 24 weeks. The investigators excluded patients who had received other tumor necrosis factor-α antagonists prior to the trial. Methotrexate and other drugs were kept at the same dosages as before the trial.

At the end of the trial, the percentage of patients who maintained remission on the Disease Activity Score was similar in the lower-dose (73%, 38 of 52) and standard-dose groups (89%, 47 of 53), said Dr. Punzi of the rheumatology unit in the department of clinical and experimental medicine at the University of Padua (Italy).

All of the 14 patients in the lower-dose group who did not maintain remission and withdrew from the trial because of a lack of efficacy returned to the standard dose; 9 (64%) of them again achieved remission, whereas the other 5 switched to another anti-TNF-α drug.

Scores on the Health Assessment Questionnaire also did not differ significantly between the groups at 8, 16, and 24 weeks. Adverse events, including serious infections, occurred at similar rates in each group.

BARCELONA, SPAIN — Rheumatoid arthritis patients in remission while taking the standard dose of etanercept may be able to switch to a lower dosing regimen and still maintain remission, Dr. Leonardo Punzi reported at the annual European Congress of Rheumatology.

He presented the results of a single-center trial. He looked at 105 adult rheumatoid arthritis (RA) patients who had maintained a Disease Activity Score of less than 1.6 for at least 6 months (defined as remission) on the standard dose of etanercept (Enbrel) in combination with a methotrexate regimen (7.5–10 mg/week). The patients were randomized to receive either a continuation of the standard dose of etanercept (25 mg twice per week) or a lower dose of the drug (25 mg once per week) for 24 weeks. The investigators excluded patients who had received other tumor necrosis factor-α antagonists prior to the trial. Methotrexate and other drugs were kept at the same dosages as before the trial.

At the end of the trial, the percentage of patients who maintained remission on the Disease Activity Score was similar in the lower-dose (73%, 38 of 52) and standard-dose groups (89%, 47 of 53), said Dr. Punzi of the rheumatology unit in the department of clinical and experimental medicine at the University of Padua (Italy).

All of the 14 patients in the lower-dose group who did not maintain remission and withdrew from the trial because of a lack of efficacy returned to the standard dose; 9 (64%) of them again achieved remission, whereas the other 5 switched to another anti-TNF-α drug.

Scores on the Health Assessment Questionnaire also did not differ significantly between the groups at 8, 16, and 24 weeks. Adverse events, including serious infections, occurred at similar rates in each group.

BARCELONA — Cumulative improvements were seen in rheumatoid arthritis patients treated with abatacept, Dr. Maxime Dougados reported at the annual European Congress of Rheumatology.

The Abatacept in Inadequate responders to Methotrexate (AIM) trial was 1 year, double blind, and placebo controlled. RA patients, mean age 51 years, were randomized to intravenous abatacept (10 mg/kg) or placebo on days 1, 15, and 29 and every 4 weeks after, plus background methotrexate. In a subsequent open-label phase, all patients received abatacept for up to 2 years. Among the 652 patients in the first phase, 385 (89%) in the abatacept group completed the 1-year treatment, versus 162 (74%) in the placebo group. Moreover, a significantly greater proportion of abatacept patients achieved an American College of Rheumatology (ACR) 20, 50, or 70 at 1 year than patients on placebo (Ann. Intern. Med. 2006;144:865-76).

Of those who had an ACR 20 at 6 months, 43% of abatacept patients had at least an ACR 50 at 1 year, versus 14% of placebo patients. The proportion who had an ACR 70 at 1 year was 21% in the abatacept group and 2% in the placebo group. A total of 15% of abatacept patients who achieved an ACR 20 at 6 months lost this response at 1 year, as did 37% of placebo patients. Significantly more patients on abatacept also achieved a low disease activity score (LDAS), of 3.2 or less. A total of 43% of abatacept patients achieved this, versus 10% of placebo patients. Of those who had an LDAS at 6 months, 36% of abatacept-treated patients and no placebo-treated patients achieved a DAS28 remission at 1 year. Thirty-two percent of abatacept patients had an LDAS at 6 months but not 1 year, versus 57% of placebo patients.

AIM was sponsored by Bristol-Myers Squibb.

BARCELONA — Cumulative improvements were seen in rheumatoid arthritis patients treated with abatacept, Dr. Maxime Dougados reported at the annual European Congress of Rheumatology.

The Abatacept in Inadequate responders to Methotrexate (AIM) trial was 1 year, double blind, and placebo controlled. RA patients, mean age 51 years, were randomized to intravenous abatacept (10 mg/kg) or placebo on days 1, 15, and 29 and every 4 weeks after, plus background methotrexate. In a subsequent open-label phase, all patients received abatacept for up to 2 years. Among the 652 patients in the first phase, 385 (89%) in the abatacept group completed the 1-year treatment, versus 162 (74%) in the placebo group. Moreover, a significantly greater proportion of abatacept patients achieved an American College of Rheumatology (ACR) 20, 50, or 70 at 1 year than patients on placebo (Ann. Intern. Med. 2006;144:865-76).

Of those who had an ACR 20 at 6 months, 43% of abatacept patients had at least an ACR 50 at 1 year, versus 14% of placebo patients. The proportion who had an ACR 70 at 1 year was 21% in the abatacept group and 2% in the placebo group. A total of 15% of abatacept patients who achieved an ACR 20 at 6 months lost this response at 1 year, as did 37% of placebo patients. Significantly more patients on abatacept also achieved a low disease activity score (LDAS), of 3.2 or less. A total of 43% of abatacept patients achieved this, versus 10% of placebo patients. Of those who had an LDAS at 6 months, 36% of abatacept-treated patients and no placebo-treated patients achieved a DAS28 remission at 1 year. Thirty-two percent of abatacept patients had an LDAS at 6 months but not 1 year, versus 57% of placebo patients.

AIM was sponsored by Bristol-Myers Squibb.

BARCELONA — Cumulative improvements were seen in rheumatoid arthritis patients treated with abatacept, Dr. Maxime Dougados reported at the annual European Congress of Rheumatology.

The Abatacept in Inadequate responders to Methotrexate (AIM) trial was 1 year, double blind, and placebo controlled. RA patients, mean age 51 years, were randomized to intravenous abatacept (10 mg/kg) or placebo on days 1, 15, and 29 and every 4 weeks after, plus background methotrexate. In a subsequent open-label phase, all patients received abatacept for up to 2 years. Among the 652 patients in the first phase, 385 (89%) in the abatacept group completed the 1-year treatment, versus 162 (74%) in the placebo group. Moreover, a significantly greater proportion of abatacept patients achieved an American College of Rheumatology (ACR) 20, 50, or 70 at 1 year than patients on placebo (Ann. Intern. Med. 2006;144:865-76).

Of those who had an ACR 20 at 6 months, 43% of abatacept patients had at least an ACR 50 at 1 year, versus 14% of placebo patients. The proportion who had an ACR 70 at 1 year was 21% in the abatacept group and 2% in the placebo group. A total of 15% of abatacept patients who achieved an ACR 20 at 6 months lost this response at 1 year, as did 37% of placebo patients. Significantly more patients on abatacept also achieved a low disease activity score (LDAS), of 3.2 or less. A total of 43% of abatacept patients achieved this, versus 10% of placebo patients. Of those who had an LDAS at 6 months, 36% of abatacept-treated patients and no placebo-treated patients achieved a DAS28 remission at 1 year. Thirty-two percent of abatacept patients had an LDAS at 6 months but not 1 year, versus 57% of placebo patients.

AIM was sponsored by Bristol-Myers Squibb.

An urgent brain CT was ordered but appeared normal.

A cervical spine radiograph showed an increased atlantoaxial (C1-C2) distance of 5 mm.

However, MRI showed a septic arthritis from C1-C2 with enhancement of the dura.

There was no evidence of bony destruction or spinal cord compression.

Although any infectious agent may cause arthritis, bacterial pathogens are the most significant because of their rapidly destructive nature.

For this reason, the current discussion concentrates on bacterial septic arthritides.

Failure to recognize and to appropriately treat septic arthritis significantly increases morbidity and may even lead to death.

According to Dr. Sarah Westlake, who is a rheumatology specialist registrar at Queen Alexandra Hospital in Portsmouth, (England), only two patients previously have been described with C1-C2 septic arthritis.

“As in our patient, early radiograph features of prevertebral soft tissue swelling can be very subtle and bony destruction of septic arthritis or endplate destruction of diskitis can take 2-8 weeks to evolve,” she said.

Cervical septic arthritis or diskitis can be life threatening. That is because there is a heightened risk of cervical spine subluxation as well as medullary compression.

“It should therefore be considered in any patient with sepsis and severe neck pain, even with normal cervical spine radiographs,” she explained.

MRI and blood cultures are the diagnostic tests of choice.

However, if the blood cultures turn out to be negative, diskovertebral biopsy for diskitis or joint aspiration for septic arthritis could be considered by a suitably-trained radiologist, said Dr. Westlake.

Blood cultures were performed on this patient on three separate occasions. The subsequent cultures grew methicillin-resistant S. aureus.

“S. aureus is the most common organism causing nongonococcal arthritis. The virulence of S. aureus is associated with its ability to attach to host tissue within the joint, evade host defenses, and cause damage to the joint,” according to Kelley's Textbook of Rheumatology, 7th edition.

The patient was treated with a 6-week course of vancomycin and an additional 6 weeks of rifampicin and doxycycline.

There were no neurologic complications that occurred at any time.

Septic arthritis from C1-C2 is seen (arrow), with enhancement of the dura. Courtesy Dr. R. Hull/Dr. S. Westlake/Dr. F. Witham

An urgent brain CT was ordered but appeared normal.

A cervical spine radiograph showed an increased atlantoaxial (C1-C2) distance of 5 mm.

However, MRI showed a septic arthritis from C1-C2 with enhancement of the dura.

There was no evidence of bony destruction or spinal cord compression.

Although any infectious agent may cause arthritis, bacterial pathogens are the most significant because of their rapidly destructive nature.

For this reason, the current discussion concentrates on bacterial septic arthritides.

Failure to recognize and to appropriately treat septic arthritis significantly increases morbidity and may even lead to death.

According to Dr. Sarah Westlake, who is a rheumatology specialist registrar at Queen Alexandra Hospital in Portsmouth, (England), only two patients previously have been described with C1-C2 septic arthritis.

“As in our patient, early radiograph features of prevertebral soft tissue swelling can be very subtle and bony destruction of septic arthritis or endplate destruction of diskitis can take 2-8 weeks to evolve,” she said.

Cervical septic arthritis or diskitis can be life threatening. That is because there is a heightened risk of cervical spine subluxation as well as medullary compression.

“It should therefore be considered in any patient with sepsis and severe neck pain, even with normal cervical spine radiographs,” she explained.

MRI and blood cultures are the diagnostic tests of choice.

However, if the blood cultures turn out to be negative, diskovertebral biopsy for diskitis or joint aspiration for septic arthritis could be considered by a suitably-trained radiologist, said Dr. Westlake.

Blood cultures were performed on this patient on three separate occasions. The subsequent cultures grew methicillin-resistant S. aureus.

“S. aureus is the most common organism causing nongonococcal arthritis. The virulence of S. aureus is associated with its ability to attach to host tissue within the joint, evade host defenses, and cause damage to the joint,” according to Kelley's Textbook of Rheumatology, 7th edition.

The patient was treated with a 6-week course of vancomycin and an additional 6 weeks of rifampicin and doxycycline.

There were no neurologic complications that occurred at any time.

Septic arthritis from C1-C2 is seen (arrow), with enhancement of the dura. Courtesy Dr. R. Hull/Dr. S. Westlake/Dr. F. Witham

An urgent brain CT was ordered but appeared normal.

A cervical spine radiograph showed an increased atlantoaxial (C1-C2) distance of 5 mm.

However, MRI showed a septic arthritis from C1-C2 with enhancement of the dura.

There was no evidence of bony destruction or spinal cord compression.

Although any infectious agent may cause arthritis, bacterial pathogens are the most significant because of their rapidly destructive nature.

For this reason, the current discussion concentrates on bacterial septic arthritides.

Failure to recognize and to appropriately treat septic arthritis significantly increases morbidity and may even lead to death.

According to Dr. Sarah Westlake, who is a rheumatology specialist registrar at Queen Alexandra Hospital in Portsmouth, (England), only two patients previously have been described with C1-C2 septic arthritis.

“As in our patient, early radiograph features of prevertebral soft tissue swelling can be very subtle and bony destruction of septic arthritis or endplate destruction of diskitis can take 2-8 weeks to evolve,” she said.

Cervical septic arthritis or diskitis can be life threatening. That is because there is a heightened risk of cervical spine subluxation as well as medullary compression.

“It should therefore be considered in any patient with sepsis and severe neck pain, even with normal cervical spine radiographs,” she explained.

MRI and blood cultures are the diagnostic tests of choice.

However, if the blood cultures turn out to be negative, diskovertebral biopsy for diskitis or joint aspiration for septic arthritis could be considered by a suitably-trained radiologist, said Dr. Westlake.

Blood cultures were performed on this patient on three separate occasions. The subsequent cultures grew methicillin-resistant S. aureus.

“S. aureus is the most common organism causing nongonococcal arthritis. The virulence of S. aureus is associated with its ability to attach to host tissue within the joint, evade host defenses, and cause damage to the joint,” according to Kelley's Textbook of Rheumatology, 7th edition.

The patient was treated with a 6-week course of vancomycin and an additional 6 weeks of rifampicin and doxycycline.

There were no neurologic complications that occurred at any time.

Septic arthritis from C1-C2 is seen (arrow), with enhancement of the dura. Courtesy Dr. R. Hull/Dr. S. Westlake/Dr. F. Witham

Professed patient satisfaction with their current rheumatoid arthritis therapy had less to do with actual therapeutic success than the fact that their disease did not worsen while on a given treatment, according to the findings of a large survey.

In their survey of 6,135 rheumatoid arthritis (RA) patients in the United States, Dr. Frederick Wolfe and Kaleb Michaud, Ph.D., both of the National Data Bank for Rheumatic Disease, in Wichita, Kan., found that overall, 66% of patients did not think there was a better treatment than what they were currently receiving; of those patients not receiving biologic agents (part of the recommended aggressive multidrug therapy for optimal RA treatment), the number was 58%.

The survey, conducted in January 2006, involved a 28-page questionnaire that assessed sociodemographic data as well as disease severity, disease duration, and past and present RA treatment. Median participant age was 62.7 years; median RA duration was 15 years. Nearly 80% were female.

Overall, roughly 64% said they would not want to change therapy unless their condition worsened. Of those, 87% cited a fear of side effects as a reason why they wouldn't switch therapies; fear of losing control if the new treatments didn't work was cited by 81%; and the belief that there were no better drugs for their disease was given by 76% of patients. The roughly two-thirds of patients who reported side effects to an arthritis drug at some point in their lifetime were least likely to be willing to change therapy (OR 1.8) and most likely to be concerned about the risk of side effects with a therapy switch (OR 1.2).

Despite patients' professed unwillingness to switch, 71% of patients who said they were satisfied with their treatment had moderate or greater arthritis activity on the Patient Activity Score, and 47% had Health Assessment Questionnaire scores greater than 1.0, which correlates with a severe disease rating, they reported (Arthritis Rheum. 2007;56:2135-42).

“Given relatively stable RA and prior experience with RA treatments, maintenance of current status [not getting worse] appears to be given high priority by patients,” wrote the investigators. They added that although cost of new drugs, inconvenience, and potential administrative hassles with their insurance carrier also contributed to patients' unwillingness to try potentially better, new therapies, “they played a small role in thinking about therapies,” compared with fear of side effects and fear of losing control, which led patients with even severe disease to resist switching therapies. “Patients' reluctance [to change therapy] may contain wisdom about homeostasis that goes beyond the experimentation of clinical trials and that is based on experience and preferences for the future. The idea of 'not getting worse' may be an important outcome that has not been considered sufficiently in therapeutic decision making.”

Dr. Wolfe acknowledged that the National Data Bank, a nonprofit research data bank, has received pharmaceutical support in the past, but the current study was independent.

Professed patient satisfaction with their current rheumatoid arthritis therapy had less to do with actual therapeutic success than the fact that their disease did not worsen while on a given treatment, according to the findings of a large survey.

In their survey of 6,135 rheumatoid arthritis (RA) patients in the United States, Dr. Frederick Wolfe and Kaleb Michaud, Ph.D., both of the National Data Bank for Rheumatic Disease, in Wichita, Kan., found that overall, 66% of patients did not think there was a better treatment than what they were currently receiving; of those patients not receiving biologic agents (part of the recommended aggressive multidrug therapy for optimal RA treatment), the number was 58%.

The survey, conducted in January 2006, involved a 28-page questionnaire that assessed sociodemographic data as well as disease severity, disease duration, and past and present RA treatment. Median participant age was 62.7 years; median RA duration was 15 years. Nearly 80% were female.

Overall, roughly 64% said they would not want to change therapy unless their condition worsened. Of those, 87% cited a fear of side effects as a reason why they wouldn't switch therapies; fear of losing control if the new treatments didn't work was cited by 81%; and the belief that there were no better drugs for their disease was given by 76% of patients. The roughly two-thirds of patients who reported side effects to an arthritis drug at some point in their lifetime were least likely to be willing to change therapy (OR 1.8) and most likely to be concerned about the risk of side effects with a therapy switch (OR 1.2).

Despite patients' professed unwillingness to switch, 71% of patients who said they were satisfied with their treatment had moderate or greater arthritis activity on the Patient Activity Score, and 47% had Health Assessment Questionnaire scores greater than 1.0, which correlates with a severe disease rating, they reported (Arthritis Rheum. 2007;56:2135-42).

“Given relatively stable RA and prior experience with RA treatments, maintenance of current status [not getting worse] appears to be given high priority by patients,” wrote the investigators. They added that although cost of new drugs, inconvenience, and potential administrative hassles with their insurance carrier also contributed to patients' unwillingness to try potentially better, new therapies, “they played a small role in thinking about therapies,” compared with fear of side effects and fear of losing control, which led patients with even severe disease to resist switching therapies. “Patients' reluctance [to change therapy] may contain wisdom about homeostasis that goes beyond the experimentation of clinical trials and that is based on experience and preferences for the future. The idea of 'not getting worse' may be an important outcome that has not been considered sufficiently in therapeutic decision making.”

Dr. Wolfe acknowledged that the National Data Bank, a nonprofit research data bank, has received pharmaceutical support in the past, but the current study was independent.

Professed patient satisfaction with their current rheumatoid arthritis therapy had less to do with actual therapeutic success than the fact that their disease did not worsen while on a given treatment, according to the findings of a large survey.

In their survey of 6,135 rheumatoid arthritis (RA) patients in the United States, Dr. Frederick Wolfe and Kaleb Michaud, Ph.D., both of the National Data Bank for Rheumatic Disease, in Wichita, Kan., found that overall, 66% of patients did not think there was a better treatment than what they were currently receiving; of those patients not receiving biologic agents (part of the recommended aggressive multidrug therapy for optimal RA treatment), the number was 58%.

The survey, conducted in January 2006, involved a 28-page questionnaire that assessed sociodemographic data as well as disease severity, disease duration, and past and present RA treatment. Median participant age was 62.7 years; median RA duration was 15 years. Nearly 80% were female.

Overall, roughly 64% said they would not want to change therapy unless their condition worsened. Of those, 87% cited a fear of side effects as a reason why they wouldn't switch therapies; fear of losing control if the new treatments didn't work was cited by 81%; and the belief that there were no better drugs for their disease was given by 76% of patients. The roughly two-thirds of patients who reported side effects to an arthritis drug at some point in their lifetime were least likely to be willing to change therapy (OR 1.8) and most likely to be concerned about the risk of side effects with a therapy switch (OR 1.2).

Despite patients' professed unwillingness to switch, 71% of patients who said they were satisfied with their treatment had moderate or greater arthritis activity on the Patient Activity Score, and 47% had Health Assessment Questionnaire scores greater than 1.0, which correlates with a severe disease rating, they reported (Arthritis Rheum. 2007;56:2135-42).

“Given relatively stable RA and prior experience with RA treatments, maintenance of current status [not getting worse] appears to be given high priority by patients,” wrote the investigators. They added that although cost of new drugs, inconvenience, and potential administrative hassles with their insurance carrier also contributed to patients' unwillingness to try potentially better, new therapies, “they played a small role in thinking about therapies,” compared with fear of side effects and fear of losing control, which led patients with even severe disease to resist switching therapies. “Patients' reluctance [to change therapy] may contain wisdom about homeostasis that goes beyond the experimentation of clinical trials and that is based on experience and preferences for the future. The idea of 'not getting worse' may be an important outcome that has not been considered sufficiently in therapeutic decision making.”

Dr. Wolfe acknowledged that the National Data Bank, a nonprofit research data bank, has received pharmaceutical support in the past, but the current study was independent.