Rheumatoid Arthritis

Major Finding: Based on a composite index for measuring the impact of RA, pain ranked highest at 21% followed by functional disability at 16% and fatigue at 15%.

Data Source: Rankings from 100 patients, 10 patients in 10 countries, on the Rheumatoid Arthritis Impact of Disease scoring system.

Disclosures: The investigators reported no relevant disclosures.

By collapsing seven health domains into one composite index, the patient-derived Rheumatoid Arthritis Impact of Disease score “allows easy assessment of the patient's perspective both for clinical trials and practice,” according to Dr. Laure Gossec of Hôpital Cochin in Paris.

The Rheumatoid Arthritis Impact of Disease (RAID) scoring system is designed to measure the impact of rheumatoid arthritis (RA) on patients' lives. The score contains components to assess perceived pain, functional disability, fatigue, emotional well-being, physical well-being, sleep disturbance, and coping. The RAID score is meant to enhance the assessment of disease status, progression, and treatment response obtained through existing disease-activity and composite indices. In essence, it is an attempt to quantify the experience of living with RA, Dr. Gossec explained in an interview.

To develop the composite response index, the principal investigators convened a steering committee comprising rheumatologists from 10 European countries along with 10 RA patients from each of the countries. Through a series of focus group sessions, the committee identified 17 areas of health that would be relevant for inclusion in the score based on an extensive literature review and the patients' personal experience, Dr. Gossec and her associates explained (Ann. Rheum. Dis. 2009;68:1680-5).

To reduce the number of domains that would be included in the final outcome measure, the steering committee devised a ranking strategy whereby 100 patients with RA (10 from each country) were asked to rank the domains on a 1-17 scale, with 1 being the most important and 17 being the least important, from their own disease experience, according to the authors. “The seven highest-ranked domains were retained in the RAID score,” they wrote.

To determine the relative importance of the top seven health domains, an additional 505 RA patients (approximately 50 from each country) were asked to distribute 100 points across the domains according to their relative impact.

Based on these rankings, mean and median ranks were computed for the entire group of patients and linearly transformed to a 0-100 range, which became the basis for the final weights, the authors reported.

The mean age and disease duration of the patients participating in the weighting process was 56 years and 15 years, respectively. Additionally, the group's mean Health Assessment Questionnaire (HAQ) score was 1.23, the authors wrote. The relative ranked weights of the seven health domains for aggregation into a composite score were 21% for pain, 16% for functional disability, 15% for fatigue, and 12% each for emotional well-being, sleep, coping, and physical well-being, they stated.

“The final selection of domains is in keeping with the published qualitative literature as pain, functional disability, and fatigue appear to be of utmost importance to many patients and were the first three domains in the ranking process,” they noted.

An analysis of the domain rankings by country determined that the patient-perceived impact of RA was similar across different countries, as well as across different patient and disease characteristics, both of which strengthen “the relevance and generalisability of the preliminary RAID score,” the authors wrote.

To measure each of the candidate domains, the steering committee, principal investigators, and two external experts selected a simple question and, when possible, a more complete validated instrument or questionnaire.

Because not all of the patient-prioritized domains are easy to measure—well-being, for example, is not readily assessable—the group elaborated specific questions, and because some domains (such as functional disability) lacked a consensus regarding which of the multiple available questionnaires was most appropriate, more than one instrument was included, the authors wrote.

“In all, 12 instruments were selected for the seven domains,” they said, noting that the final choice of one instrument per domain will be made after ongoing validation study of the RAID score.

The measure is currently being implemented in at least three ongoing clinical trials and at least one cohort, said Dr. Gossec.

Major Finding: Based on a composite index for measuring the impact of RA, pain ranked highest at 21% followed by functional disability at 16% and fatigue at 15%.

Data Source: Rankings from 100 patients, 10 patients in 10 countries, on the Rheumatoid Arthritis Impact of Disease scoring system.

Disclosures: The investigators reported no relevant disclosures.

By collapsing seven health domains into one composite index, the patient-derived Rheumatoid Arthritis Impact of Disease score “allows easy assessment of the patient's perspective both for clinical trials and practice,” according to Dr. Laure Gossec of Hôpital Cochin in Paris.

The Rheumatoid Arthritis Impact of Disease (RAID) scoring system is designed to measure the impact of rheumatoid arthritis (RA) on patients' lives. The score contains components to assess perceived pain, functional disability, fatigue, emotional well-being, physical well-being, sleep disturbance, and coping. The RAID score is meant to enhance the assessment of disease status, progression, and treatment response obtained through existing disease-activity and composite indices. In essence, it is an attempt to quantify the experience of living with RA, Dr. Gossec explained in an interview.

To develop the composite response index, the principal investigators convened a steering committee comprising rheumatologists from 10 European countries along with 10 RA patients from each of the countries. Through a series of focus group sessions, the committee identified 17 areas of health that would be relevant for inclusion in the score based on an extensive literature review and the patients' personal experience, Dr. Gossec and her associates explained (Ann. Rheum. Dis. 2009;68:1680-5).

To reduce the number of domains that would be included in the final outcome measure, the steering committee devised a ranking strategy whereby 100 patients with RA (10 from each country) were asked to rank the domains on a 1-17 scale, with 1 being the most important and 17 being the least important, from their own disease experience, according to the authors. “The seven highest-ranked domains were retained in the RAID score,” they wrote.

To determine the relative importance of the top seven health domains, an additional 505 RA patients (approximately 50 from each country) were asked to distribute 100 points across the domains according to their relative impact.

Based on these rankings, mean and median ranks were computed for the entire group of patients and linearly transformed to a 0-100 range, which became the basis for the final weights, the authors reported.

The mean age and disease duration of the patients participating in the weighting process was 56 years and 15 years, respectively. Additionally, the group's mean Health Assessment Questionnaire (HAQ) score was 1.23, the authors wrote. The relative ranked weights of the seven health domains for aggregation into a composite score were 21% for pain, 16% for functional disability, 15% for fatigue, and 12% each for emotional well-being, sleep, coping, and physical well-being, they stated.

“The final selection of domains is in keeping with the published qualitative literature as pain, functional disability, and fatigue appear to be of utmost importance to many patients and were the first three domains in the ranking process,” they noted.

An analysis of the domain rankings by country determined that the patient-perceived impact of RA was similar across different countries, as well as across different patient and disease characteristics, both of which strengthen “the relevance and generalisability of the preliminary RAID score,” the authors wrote.

To measure each of the candidate domains, the steering committee, principal investigators, and two external experts selected a simple question and, when possible, a more complete validated instrument or questionnaire.

Because not all of the patient-prioritized domains are easy to measure—well-being, for example, is not readily assessable—the group elaborated specific questions, and because some domains (such as functional disability) lacked a consensus regarding which of the multiple available questionnaires was most appropriate, more than one instrument was included, the authors wrote.

“In all, 12 instruments were selected for the seven domains,” they said, noting that the final choice of one instrument per domain will be made after ongoing validation study of the RAID score.

The measure is currently being implemented in at least three ongoing clinical trials and at least one cohort, said Dr. Gossec.

Major Finding: Based on a composite index for measuring the impact of RA, pain ranked highest at 21% followed by functional disability at 16% and fatigue at 15%.

Data Source: Rankings from 100 patients, 10 patients in 10 countries, on the Rheumatoid Arthritis Impact of Disease scoring system.

Disclosures: The investigators reported no relevant disclosures.

By collapsing seven health domains into one composite index, the patient-derived Rheumatoid Arthritis Impact of Disease score “allows easy assessment of the patient's perspective both for clinical trials and practice,” according to Dr. Laure Gossec of Hôpital Cochin in Paris.

The Rheumatoid Arthritis Impact of Disease (RAID) scoring system is designed to measure the impact of rheumatoid arthritis (RA) on patients' lives. The score contains components to assess perceived pain, functional disability, fatigue, emotional well-being, physical well-being, sleep disturbance, and coping. The RAID score is meant to enhance the assessment of disease status, progression, and treatment response obtained through existing disease-activity and composite indices. In essence, it is an attempt to quantify the experience of living with RA, Dr. Gossec explained in an interview.

To develop the composite response index, the principal investigators convened a steering committee comprising rheumatologists from 10 European countries along with 10 RA patients from each of the countries. Through a series of focus group sessions, the committee identified 17 areas of health that would be relevant for inclusion in the score based on an extensive literature review and the patients' personal experience, Dr. Gossec and her associates explained (Ann. Rheum. Dis. 2009;68:1680-5).

To reduce the number of domains that would be included in the final outcome measure, the steering committee devised a ranking strategy whereby 100 patients with RA (10 from each country) were asked to rank the domains on a 1-17 scale, with 1 being the most important and 17 being the least important, from their own disease experience, according to the authors. “The seven highest-ranked domains were retained in the RAID score,” they wrote.

To determine the relative importance of the top seven health domains, an additional 505 RA patients (approximately 50 from each country) were asked to distribute 100 points across the domains according to their relative impact.

Based on these rankings, mean and median ranks were computed for the entire group of patients and linearly transformed to a 0-100 range, which became the basis for the final weights, the authors reported.

The mean age and disease duration of the patients participating in the weighting process was 56 years and 15 years, respectively. Additionally, the group's mean Health Assessment Questionnaire (HAQ) score was 1.23, the authors wrote. The relative ranked weights of the seven health domains for aggregation into a composite score were 21% for pain, 16% for functional disability, 15% for fatigue, and 12% each for emotional well-being, sleep, coping, and physical well-being, they stated.

“The final selection of domains is in keeping with the published qualitative literature as pain, functional disability, and fatigue appear to be of utmost importance to many patients and were the first three domains in the ranking process,” they noted.

An analysis of the domain rankings by country determined that the patient-perceived impact of RA was similar across different countries, as well as across different patient and disease characteristics, both of which strengthen “the relevance and generalisability of the preliminary RAID score,” the authors wrote.

To measure each of the candidate domains, the steering committee, principal investigators, and two external experts selected a simple question and, when possible, a more complete validated instrument or questionnaire.

Because not all of the patient-prioritized domains are easy to measure—well-being, for example, is not readily assessable—the group elaborated specific questions, and because some domains (such as functional disability) lacked a consensus regarding which of the multiple available questionnaires was most appropriate, more than one instrument was included, the authors wrote.

“In all, 12 instruments were selected for the seven domains,” they said, noting that the final choice of one instrument per domain will be made after ongoing validation study of the RAID score.

The measure is currently being implemented in at least three ongoing clinical trials and at least one cohort, said Dr. Gossec.

SNOWMASS, COLO. — You may be confident that you've got great hands for performing joint injections and aspirations, but the scientific evidence shows that unless you're using sonographic needle guidance, you're not nearly as good as you think.

Numerous studies have demonstrated that even skilled rheumatologists and orthopedic surgeons fail to place their needle tip in the intra-articular space 50%-60% of the time when they use palpation to guide injections, Dr. Eric L. Matteson said at a symposium sponsored by the American College of Rheumatology.

To make his point, Dr. Matteson cited data from a recent multicenter randomized trial involving ultrasound- or palpation-guided intra-articular steroid injections of 148 painful joints (mostly knees, wrists, shoulders, hips, elbows, wrists, and ankles). The ultrasound-guided group had 44% less procedural pain and a 59% greater reduction in pain at the 2-week follow-up than did the palpation group. Sonographic needle guidance also resulted in a 337% increase in the volume of aspirated fluid (J. Rheumatol. 2009;36:892-902).

“There's no question that ultrasound-guided injections are more accurate in certain joints, such as the deeper joints like the hips, the small joints of the hands, and the subacromial bursa,” said Dr. Matteson, professor of medicine and chief of the division of rheumatology at the Mayo Clinic, Rochester, Minn.

As a practical matter, he is quick to turn to ultrasound guidance in patients who are obese, have failed prior injections or aspirations, have experienced significant pain with prior injections, or have difficulty assuming the proper position for standard injections.

Since taking up musculoskeletal ultrasound half a decade ago, Dr. Matteson said he has become a huge fan. He uses it not only to guide procedures, but also as a dynamic extension of his clinical examination. Dr. Matteson reported that in his experience, musculoskeletal ultrasound is of great assistance in the diagnosis of tendon ruptures, synovitis and tenosynovitis, bursitis, effusions, soft tissue nodules, erosions, and the assessment of disease activity.

The use of office ultrasound to assess the hip joint is particularly noteworthy. This assessment is something that otherwise would often require a referral to radiology.

Another area in which musculoskeletal ultrasound has been a real breakthrough is in assessing the cause of shoulder pain. Ultrasound can readily visualize impingement, biceps tendon dislocation, acromioclavicular and sternoclavicular joint pathology, synovitis, and bursitis, as well as adhesions, calcifications, and rupture of the rotator cuff.

“Here I think ultrasound is a great boon to us in our practice. Assessing causes of shoulder pain is really a fantastic application,” he continued.

Patients love seeing their anatomy on the ultrasound screen; it turns their office visit into an educational experience, according to Dr. Matteson. Musculoskeletal ultrasound is a great teaching tool for medical professionals, as well.

“It's something that creates excitement among the fellows and medical students and residents who rotate through,” he said.

Indeed, a move is afoot to develop a curriculum for rheumatology fellows that will enable them to demonstrate competence in the technique.

Musculoskeletal ultrasound is rather well reimbursed under CPT billing codes 76880 and 76942, which were set by radiologists. Although it's possible to spend $100,000-$200,000 on an ultrasound machine, doing so is entirely unnecessary. A very good machine can be purchased for $40,000. The major equipment manufacturers typically sell demonstration models after a year's light use for considerably less.

Ultrasound probes that cover 5-13 MHz best serve rheumatologists' purposes, providing the required balance between penetration and resolution that permits the imaging of both deep structures like the hip and superficial ones like fingers.

The U.S. rheumatologist ultrasound interest group is reachable at www.msk-uss.org

Disclosures: Dr. Matteson indicated he has no relevant financial interests.

To view an interview with Dr. Matteson, go to www.youtube.com/rheumatologynews

Ultrasound shows synovial fluid (black) with needle approaching from right in a knee aspiration in an obese patient.

Source Courtesy Dr. Eric L. Matteson

SNOWMASS, COLO. — You may be confident that you've got great hands for performing joint injections and aspirations, but the scientific evidence shows that unless you're using sonographic needle guidance, you're not nearly as good as you think.

Numerous studies have demonstrated that even skilled rheumatologists and orthopedic surgeons fail to place their needle tip in the intra-articular space 50%-60% of the time when they use palpation to guide injections, Dr. Eric L. Matteson said at a symposium sponsored by the American College of Rheumatology.

To make his point, Dr. Matteson cited data from a recent multicenter randomized trial involving ultrasound- or palpation-guided intra-articular steroid injections of 148 painful joints (mostly knees, wrists, shoulders, hips, elbows, wrists, and ankles). The ultrasound-guided group had 44% less procedural pain and a 59% greater reduction in pain at the 2-week follow-up than did the palpation group. Sonographic needle guidance also resulted in a 337% increase in the volume of aspirated fluid (J. Rheumatol. 2009;36:892-902).

“There's no question that ultrasound-guided injections are more accurate in certain joints, such as the deeper joints like the hips, the small joints of the hands, and the subacromial bursa,” said Dr. Matteson, professor of medicine and chief of the division of rheumatology at the Mayo Clinic, Rochester, Minn.

As a practical matter, he is quick to turn to ultrasound guidance in patients who are obese, have failed prior injections or aspirations, have experienced significant pain with prior injections, or have difficulty assuming the proper position for standard injections.

Since taking up musculoskeletal ultrasound half a decade ago, Dr. Matteson said he has become a huge fan. He uses it not only to guide procedures, but also as a dynamic extension of his clinical examination. Dr. Matteson reported that in his experience, musculoskeletal ultrasound is of great assistance in the diagnosis of tendon ruptures, synovitis and tenosynovitis, bursitis, effusions, soft tissue nodules, erosions, and the assessment of disease activity.

The use of office ultrasound to assess the hip joint is particularly noteworthy. This assessment is something that otherwise would often require a referral to radiology.

Another area in which musculoskeletal ultrasound has been a real breakthrough is in assessing the cause of shoulder pain. Ultrasound can readily visualize impingement, biceps tendon dislocation, acromioclavicular and sternoclavicular joint pathology, synovitis, and bursitis, as well as adhesions, calcifications, and rupture of the rotator cuff.

“Here I think ultrasound is a great boon to us in our practice. Assessing causes of shoulder pain is really a fantastic application,” he continued.

Patients love seeing their anatomy on the ultrasound screen; it turns their office visit into an educational experience, according to Dr. Matteson. Musculoskeletal ultrasound is a great teaching tool for medical professionals, as well.

“It's something that creates excitement among the fellows and medical students and residents who rotate through,” he said.

Indeed, a move is afoot to develop a curriculum for rheumatology fellows that will enable them to demonstrate competence in the technique.

Musculoskeletal ultrasound is rather well reimbursed under CPT billing codes 76880 and 76942, which were set by radiologists. Although it's possible to spend $100,000-$200,000 on an ultrasound machine, doing so is entirely unnecessary. A very good machine can be purchased for $40,000. The major equipment manufacturers typically sell demonstration models after a year's light use for considerably less.

Ultrasound probes that cover 5-13 MHz best serve rheumatologists' purposes, providing the required balance between penetration and resolution that permits the imaging of both deep structures like the hip and superficial ones like fingers.

The U.S. rheumatologist ultrasound interest group is reachable at www.msk-uss.org

Disclosures: Dr. Matteson indicated he has no relevant financial interests.

To view an interview with Dr. Matteson, go to www.youtube.com/rheumatologynews

Ultrasound shows synovial fluid (black) with needle approaching from right in a knee aspiration in an obese patient.

Source Courtesy Dr. Eric L. Matteson

SNOWMASS, COLO. — You may be confident that you've got great hands for performing joint injections and aspirations, but the scientific evidence shows that unless you're using sonographic needle guidance, you're not nearly as good as you think.

Numerous studies have demonstrated that even skilled rheumatologists and orthopedic surgeons fail to place their needle tip in the intra-articular space 50%-60% of the time when they use palpation to guide injections, Dr. Eric L. Matteson said at a symposium sponsored by the American College of Rheumatology.

To make his point, Dr. Matteson cited data from a recent multicenter randomized trial involving ultrasound- or palpation-guided intra-articular steroid injections of 148 painful joints (mostly knees, wrists, shoulders, hips, elbows, wrists, and ankles). The ultrasound-guided group had 44% less procedural pain and a 59% greater reduction in pain at the 2-week follow-up than did the palpation group. Sonographic needle guidance also resulted in a 337% increase in the volume of aspirated fluid (J. Rheumatol. 2009;36:892-902).

“There's no question that ultrasound-guided injections are more accurate in certain joints, such as the deeper joints like the hips, the small joints of the hands, and the subacromial bursa,” said Dr. Matteson, professor of medicine and chief of the division of rheumatology at the Mayo Clinic, Rochester, Minn.

As a practical matter, he is quick to turn to ultrasound guidance in patients who are obese, have failed prior injections or aspirations, have experienced significant pain with prior injections, or have difficulty assuming the proper position for standard injections.

Since taking up musculoskeletal ultrasound half a decade ago, Dr. Matteson said he has become a huge fan. He uses it not only to guide procedures, but also as a dynamic extension of his clinical examination. Dr. Matteson reported that in his experience, musculoskeletal ultrasound is of great assistance in the diagnosis of tendon ruptures, synovitis and tenosynovitis, bursitis, effusions, soft tissue nodules, erosions, and the assessment of disease activity.

The use of office ultrasound to assess the hip joint is particularly noteworthy. This assessment is something that otherwise would often require a referral to radiology.

Another area in which musculoskeletal ultrasound has been a real breakthrough is in assessing the cause of shoulder pain. Ultrasound can readily visualize impingement, biceps tendon dislocation, acromioclavicular and sternoclavicular joint pathology, synovitis, and bursitis, as well as adhesions, calcifications, and rupture of the rotator cuff.

“Here I think ultrasound is a great boon to us in our practice. Assessing causes of shoulder pain is really a fantastic application,” he continued.

Patients love seeing their anatomy on the ultrasound screen; it turns their office visit into an educational experience, according to Dr. Matteson. Musculoskeletal ultrasound is a great teaching tool for medical professionals, as well.

“It's something that creates excitement among the fellows and medical students and residents who rotate through,” he said.

Indeed, a move is afoot to develop a curriculum for rheumatology fellows that will enable them to demonstrate competence in the technique.

Musculoskeletal ultrasound is rather well reimbursed under CPT billing codes 76880 and 76942, which were set by radiologists. Although it's possible to spend $100,000-$200,000 on an ultrasound machine, doing so is entirely unnecessary. A very good machine can be purchased for $40,000. The major equipment manufacturers typically sell demonstration models after a year's light use for considerably less.

Ultrasound probes that cover 5-13 MHz best serve rheumatologists' purposes, providing the required balance between penetration and resolution that permits the imaging of both deep structures like the hip and superficial ones like fingers.

The U.S. rheumatologist ultrasound interest group is reachable at www.msk-uss.org

Disclosures: Dr. Matteson indicated he has no relevant financial interests.

To view an interview with Dr. Matteson, go to www.youtube.com/rheumatologynews

Ultrasound shows synovial fluid (black) with needle approaching from right in a knee aspiration in an obese patient.

Source Courtesy Dr. Eric L. Matteson

Every Friday, Dr. Shariar Cohen-Gadol drives 71 miles from his home in West Los Angeles to California State Prison, Los Angeles County, a 262-acre facility in Lancaster that houses more than 5,000 convicted felons, some of whom have rheumatoid arthritis, osteoarthritis, or other rheumatologic disorders. To the California prison system, these inmates need medical care despite their being held in minimum, high-medium, and maximum custody, and Dr. Cohen-Gadol is the physician who provides that care.

Dr. Cohen-Gadol described the overall rheumatologic care provided to California inmates as being better than what some managed care organizations offer. If an inmate with moderate to severe arthritis fails to respond to methotrexate, “I have no problem getting him adalimumab or etanercept,” he said.

“My recommendation may have to be reviewed by the chief medical officer at the institution. But so far, I have been impressed by how prisons have been able to provide [anti-tumor necrosis factor] agents so fast.”

The care he gives the California inmates with rheumatologic disorders is not limited to infusions of biologic agents. Dr. Cohen-Gadol does everything from giving general physical exams to administering intra-articular injections and conducting follow-up visits with those who've started therapy with anti-TNF agents or other medications.

Telemedicine also plays a roll in this care. Dr. Cohen-Gadol uses a telemedicine setup that is located in a dedicated office at the prison and provides him with access via two-way video feed to about 30 other sites in the state operated by the California Department of Corrections and Rehabilitation, a program that he helped launch nearly 2 years ago.

“We may consult with four or five institutions by telemedicine in one day,” said Dr. Cohen-Gadol, a rheumatologist who practices in Thousand Oaks. “I call in and the other health care providers appear on the TV screen. We may evaluate two inmates from one institution, or five follow-ups. I take the history and the nurse at the other end of the connection does the exam.”

He said he was drawn to the work because it broadens his clinical experience without the burden of administrative overhead. His interest in the health issues of prison populations was born during his residency at the University of California, Los Angeles, when he conducted grand rounds on the manifestations of hepatitis C. At the Lancaster facility, at least one-third of inmates are infected with the disease.

“That means that more than 1,200 have chronic hepatitis C,” he said, noting that most of the inmates he treats are in their 30s and 40s. The chronic infection seems to increase the inmates' risk for some markers of rheumatologic disorders. With hepatitis C, many patients “have antibodies for markers of lupus, like [antinuclear antibody], or markers of rheumatoid arthritis, like rheumatoid factor. It creates an enigma for the primary care doctors, so I get the referrals.”

He's seen cases of cryoglobulinemia, Raynaud's disease, exotic rashes, kidney involvement, hives, urticaria, joint pain, myalgia, and polyarthralgia associated with hepatitis C.

“One thing that increases the difficulty of providing rheumatologic care to inmates is the limitation of using certain drugs in patients with hepatitis C infection,” Dr. Cohen-Gadol commented. “A lot of drugs are immunosuppressive and are processed through the liver, like methotrexate. That makes it difficult for a patient with chronic RA. Sometimes we have to use drugs like etanercept or adalimumab because they have worse disease.

“It creates a challenge.”

If an inmate needs an intramuscular injection, the nursing staff can administer it locally. However, for intra-articular or bursa/tendon injections, an on-site physician needs to give it. “This is obviously one of the many shortcomings of telemedicine,” he said.

However, many glitches in his efforts to provide care have nothing to do with flaws of technology. “We are sometimes limited when inmates refuse care, or there are lockdowns, or they are getting paroled, or there are family visits,” Dr. Cohen-Gadol explained. “Let's say you're scheduled to see 20 patients one day. Maybe you'll see 13 or 15 patients instead. It's not perfect.”

As the only rheumatologist consultant for the California's prison system, Dr. Cohen-Gadol endures long waits, sometimes up to 4 months, for certain tests, imaging, and follow-up visits. “Patients may have to be transferred to an academic center for a biopsy.”

He went on to note that the physician-patient relationship in the prison setting is different because “you're dealing with a population you can't fully trust. Many of the patients have a history of polysubstance abuse. A large number have used cocaine, heroin, and crystal methamphetamine. Some of the patients with whom you deal are very manipulative and drug seeking. Others are rude and abusive. Some are brought in wearing shackles because of their past histories. But most of them behave pretty well because they know they need your help.”

Telemedicine works for the prison system “because it saves the taxpayers a lot of mone,” he said.

Every Friday, Dr. Shariar Cohen-Gadol drives 71 miles from his home in West Los Angeles to California State Prison, Los Angeles County, a 262-acre facility in Lancaster that houses more than 5,000 convicted felons, some of whom have rheumatoid arthritis, osteoarthritis, or other rheumatologic disorders. To the California prison system, these inmates need medical care despite their being held in minimum, high-medium, and maximum custody, and Dr. Cohen-Gadol is the physician who provides that care.

Dr. Cohen-Gadol described the overall rheumatologic care provided to California inmates as being better than what some managed care organizations offer. If an inmate with moderate to severe arthritis fails to respond to methotrexate, “I have no problem getting him adalimumab or etanercept,” he said.

“My recommendation may have to be reviewed by the chief medical officer at the institution. But so far, I have been impressed by how prisons have been able to provide [anti-tumor necrosis factor] agents so fast.”

The care he gives the California inmates with rheumatologic disorders is not limited to infusions of biologic agents. Dr. Cohen-Gadol does everything from giving general physical exams to administering intra-articular injections and conducting follow-up visits with those who've started therapy with anti-TNF agents or other medications.

Telemedicine also plays a roll in this care. Dr. Cohen-Gadol uses a telemedicine setup that is located in a dedicated office at the prison and provides him with access via two-way video feed to about 30 other sites in the state operated by the California Department of Corrections and Rehabilitation, a program that he helped launch nearly 2 years ago.

“We may consult with four or five institutions by telemedicine in one day,” said Dr. Cohen-Gadol, a rheumatologist who practices in Thousand Oaks. “I call in and the other health care providers appear on the TV screen. We may evaluate two inmates from one institution, or five follow-ups. I take the history and the nurse at the other end of the connection does the exam.”

He said he was drawn to the work because it broadens his clinical experience without the burden of administrative overhead. His interest in the health issues of prison populations was born during his residency at the University of California, Los Angeles, when he conducted grand rounds on the manifestations of hepatitis C. At the Lancaster facility, at least one-third of inmates are infected with the disease.

“That means that more than 1,200 have chronic hepatitis C,” he said, noting that most of the inmates he treats are in their 30s and 40s. The chronic infection seems to increase the inmates' risk for some markers of rheumatologic disorders. With hepatitis C, many patients “have antibodies for markers of lupus, like [antinuclear antibody], or markers of rheumatoid arthritis, like rheumatoid factor. It creates an enigma for the primary care doctors, so I get the referrals.”

He's seen cases of cryoglobulinemia, Raynaud's disease, exotic rashes, kidney involvement, hives, urticaria, joint pain, myalgia, and polyarthralgia associated with hepatitis C.

“One thing that increases the difficulty of providing rheumatologic care to inmates is the limitation of using certain drugs in patients with hepatitis C infection,” Dr. Cohen-Gadol commented. “A lot of drugs are immunosuppressive and are processed through the liver, like methotrexate. That makes it difficult for a patient with chronic RA. Sometimes we have to use drugs like etanercept or adalimumab because they have worse disease.

“It creates a challenge.”

If an inmate needs an intramuscular injection, the nursing staff can administer it locally. However, for intra-articular or bursa/tendon injections, an on-site physician needs to give it. “This is obviously one of the many shortcomings of telemedicine,” he said.

However, many glitches in his efforts to provide care have nothing to do with flaws of technology. “We are sometimes limited when inmates refuse care, or there are lockdowns, or they are getting paroled, or there are family visits,” Dr. Cohen-Gadol explained. “Let's say you're scheduled to see 20 patients one day. Maybe you'll see 13 or 15 patients instead. It's not perfect.”

As the only rheumatologist consultant for the California's prison system, Dr. Cohen-Gadol endures long waits, sometimes up to 4 months, for certain tests, imaging, and follow-up visits. “Patients may have to be transferred to an academic center for a biopsy.”

He went on to note that the physician-patient relationship in the prison setting is different because “you're dealing with a population you can't fully trust. Many of the patients have a history of polysubstance abuse. A large number have used cocaine, heroin, and crystal methamphetamine. Some of the patients with whom you deal are very manipulative and drug seeking. Others are rude and abusive. Some are brought in wearing shackles because of their past histories. But most of them behave pretty well because they know they need your help.”

Telemedicine works for the prison system “because it saves the taxpayers a lot of mone,” he said.

Every Friday, Dr. Shariar Cohen-Gadol drives 71 miles from his home in West Los Angeles to California State Prison, Los Angeles County, a 262-acre facility in Lancaster that houses more than 5,000 convicted felons, some of whom have rheumatoid arthritis, osteoarthritis, or other rheumatologic disorders. To the California prison system, these inmates need medical care despite their being held in minimum, high-medium, and maximum custody, and Dr. Cohen-Gadol is the physician who provides that care.

Dr. Cohen-Gadol described the overall rheumatologic care provided to California inmates as being better than what some managed care organizations offer. If an inmate with moderate to severe arthritis fails to respond to methotrexate, “I have no problem getting him adalimumab or etanercept,” he said.

“My recommendation may have to be reviewed by the chief medical officer at the institution. But so far, I have been impressed by how prisons have been able to provide [anti-tumor necrosis factor] agents so fast.”

The care he gives the California inmates with rheumatologic disorders is not limited to infusions of biologic agents. Dr. Cohen-Gadol does everything from giving general physical exams to administering intra-articular injections and conducting follow-up visits with those who've started therapy with anti-TNF agents or other medications.

Telemedicine also plays a roll in this care. Dr. Cohen-Gadol uses a telemedicine setup that is located in a dedicated office at the prison and provides him with access via two-way video feed to about 30 other sites in the state operated by the California Department of Corrections and Rehabilitation, a program that he helped launch nearly 2 years ago.

“We may consult with four or five institutions by telemedicine in one day,” said Dr. Cohen-Gadol, a rheumatologist who practices in Thousand Oaks. “I call in and the other health care providers appear on the TV screen. We may evaluate two inmates from one institution, or five follow-ups. I take the history and the nurse at the other end of the connection does the exam.”

He said he was drawn to the work because it broadens his clinical experience without the burden of administrative overhead. His interest in the health issues of prison populations was born during his residency at the University of California, Los Angeles, when he conducted grand rounds on the manifestations of hepatitis C. At the Lancaster facility, at least one-third of inmates are infected with the disease.

“That means that more than 1,200 have chronic hepatitis C,” he said, noting that most of the inmates he treats are in their 30s and 40s. The chronic infection seems to increase the inmates' risk for some markers of rheumatologic disorders. With hepatitis C, many patients “have antibodies for markers of lupus, like [antinuclear antibody], or markers of rheumatoid arthritis, like rheumatoid factor. It creates an enigma for the primary care doctors, so I get the referrals.”

He's seen cases of cryoglobulinemia, Raynaud's disease, exotic rashes, kidney involvement, hives, urticaria, joint pain, myalgia, and polyarthralgia associated with hepatitis C.

“One thing that increases the difficulty of providing rheumatologic care to inmates is the limitation of using certain drugs in patients with hepatitis C infection,” Dr. Cohen-Gadol commented. “A lot of drugs are immunosuppressive and are processed through the liver, like methotrexate. That makes it difficult for a patient with chronic RA. Sometimes we have to use drugs like etanercept or adalimumab because they have worse disease.

“It creates a challenge.”

If an inmate needs an intramuscular injection, the nursing staff can administer it locally. However, for intra-articular or bursa/tendon injections, an on-site physician needs to give it. “This is obviously one of the many shortcomings of telemedicine,” he said.

However, many glitches in his efforts to provide care have nothing to do with flaws of technology. “We are sometimes limited when inmates refuse care, or there are lockdowns, or they are getting paroled, or there are family visits,” Dr. Cohen-Gadol explained. “Let's say you're scheduled to see 20 patients one day. Maybe you'll see 13 or 15 patients instead. It's not perfect.”

As the only rheumatologist consultant for the California's prison system, Dr. Cohen-Gadol endures long waits, sometimes up to 4 months, for certain tests, imaging, and follow-up visits. “Patients may have to be transferred to an academic center for a biopsy.”

He went on to note that the physician-patient relationship in the prison setting is different because “you're dealing with a population you can't fully trust. Many of the patients have a history of polysubstance abuse. A large number have used cocaine, heroin, and crystal methamphetamine. Some of the patients with whom you deal are very manipulative and drug seeking. Others are rude and abusive. Some are brought in wearing shackles because of their past histories. But most of them behave pretty well because they know they need your help.”

Telemedicine works for the prison system “because it saves the taxpayers a lot of mone,” he said.

Major Finding: More than half of patients with JIA who were transferred to an adult rheumatologist received inadequate follow-up at 2 years.

Data Source: Chart review of 100 patients with JIA.

Disclosures: The researchers disclosed having no relevant financial conflicts.

More than half of patients with juvenile idiopathic arthritis who transferred to an adult rheumatologist had inadequate follow-up for their disease 2 years after being transferred, judging from results of a Canadian study.

“Every effort should be made to ensure that young adults with JIA have timely access to a rheumatologist in the event of a disease flare, in order to minimize their disease burden,” researchers led by Dr. Elizabeth M. Hazel, an adult rheumatologist at McGill University Health Centre in Montreal, wrote in a study published online in Pediatric Rheumatology.

In the first published analysis of its kind, the researchers conducted a systematic chart review of 100 patients with JIA who attended their final JIA clinic appointment at Montreal Children's Hospital between 1992 and 2005 when they were aged 17 years or older. More than two-thirds of the patients (68%) were female, and the mean age of disease onset was 9.84 years (Pediatr. Rheumatol. 2010 Jan. 11 [doi:10.1186/1546-0096-8-2]).

“Once the name of the adult rheumatologist was identified in the transfer letter, or the last clinic note, his/her office was contacted for permission for a chart review to be conducted,” the researchers explained. The chart was then reviewed for 2 years after transfer.

A patient was deemed to have had an unsuccessful transfer if he or she “never made contact with the identified adult rheumatologist or was lost to follow-up at 2 years following transfer.”

Dr. Hazel and her associates also compared a number of factors among patients who did and did not have successful transfers, including sex, category of JIA, age at diagnosis, use of disease-modifying antirheumatic agents, active joint count, and level of educational attainment.

Of the 100 patients, 52 (52%) met the criteria for unsuccessful transfer from pediatric to adult care. Of these, 17 (33%) did not make initial contact with the appointed adult rheumatologist and 35 (67%) were lost to follow-up at 2 years.

“I was very surprised that more than half of the patients were lost to follow-up,” Dr. Hazel commented in an interview.

Of the patient factors tested, only one was significantly associated with unsuccessful patient transfer: an active joint count of zero at the last visit (odds ratio, 2.67). “This group of young adults with relatively inactive disease should be educated about the importance of ongoing follow-up in the adult milieu given the high possibility of active disease into adulthood,” the researchers advised.

Male sex trended toward a higher risk for unsuccessful transfer (OR, 2.15).

In her interview, Dr. Hazel acknowledged certain limitations of the study, including its retrospective cohort design. “This was a chart review, so we were limited by the information recorded in the charts,” she said.

“We could not track patients who sought out other rheumatologists on their own if they did not request a transfer letter from the pediatric group. While this may have improved the rate of transfer, these cases would still represent a suboptimal situation, with the adult rheumatologist not having information about the pediatric course of illness.”

Major Finding: More than half of patients with JIA who were transferred to an adult rheumatologist received inadequate follow-up at 2 years.

Data Source: Chart review of 100 patients with JIA.

Disclosures: The researchers disclosed having no relevant financial conflicts.

More than half of patients with juvenile idiopathic arthritis who transferred to an adult rheumatologist had inadequate follow-up for their disease 2 years after being transferred, judging from results of a Canadian study.

“Every effort should be made to ensure that young adults with JIA have timely access to a rheumatologist in the event of a disease flare, in order to minimize their disease burden,” researchers led by Dr. Elizabeth M. Hazel, an adult rheumatologist at McGill University Health Centre in Montreal, wrote in a study published online in Pediatric Rheumatology.

In the first published analysis of its kind, the researchers conducted a systematic chart review of 100 patients with JIA who attended their final JIA clinic appointment at Montreal Children's Hospital between 1992 and 2005 when they were aged 17 years or older. More than two-thirds of the patients (68%) were female, and the mean age of disease onset was 9.84 years (Pediatr. Rheumatol. 2010 Jan. 11 [doi:10.1186/1546-0096-8-2]).

“Once the name of the adult rheumatologist was identified in the transfer letter, or the last clinic note, his/her office was contacted for permission for a chart review to be conducted,” the researchers explained. The chart was then reviewed for 2 years after transfer.

A patient was deemed to have had an unsuccessful transfer if he or she “never made contact with the identified adult rheumatologist or was lost to follow-up at 2 years following transfer.”

Dr. Hazel and her associates also compared a number of factors among patients who did and did not have successful transfers, including sex, category of JIA, age at diagnosis, use of disease-modifying antirheumatic agents, active joint count, and level of educational attainment.

Of the 100 patients, 52 (52%) met the criteria for unsuccessful transfer from pediatric to adult care. Of these, 17 (33%) did not make initial contact with the appointed adult rheumatologist and 35 (67%) were lost to follow-up at 2 years.

“I was very surprised that more than half of the patients were lost to follow-up,” Dr. Hazel commented in an interview.

Of the patient factors tested, only one was significantly associated with unsuccessful patient transfer: an active joint count of zero at the last visit (odds ratio, 2.67). “This group of young adults with relatively inactive disease should be educated about the importance of ongoing follow-up in the adult milieu given the high possibility of active disease into adulthood,” the researchers advised.

Male sex trended toward a higher risk for unsuccessful transfer (OR, 2.15).

In her interview, Dr. Hazel acknowledged certain limitations of the study, including its retrospective cohort design. “This was a chart review, so we were limited by the information recorded in the charts,” she said.

“We could not track patients who sought out other rheumatologists on their own if they did not request a transfer letter from the pediatric group. While this may have improved the rate of transfer, these cases would still represent a suboptimal situation, with the adult rheumatologist not having information about the pediatric course of illness.”

Major Finding: More than half of patients with JIA who were transferred to an adult rheumatologist received inadequate follow-up at 2 years.

Data Source: Chart review of 100 patients with JIA.

Disclosures: The researchers disclosed having no relevant financial conflicts.

More than half of patients with juvenile idiopathic arthritis who transferred to an adult rheumatologist had inadequate follow-up for their disease 2 years after being transferred, judging from results of a Canadian study.

“Every effort should be made to ensure that young adults with JIA have timely access to a rheumatologist in the event of a disease flare, in order to minimize their disease burden,” researchers led by Dr. Elizabeth M. Hazel, an adult rheumatologist at McGill University Health Centre in Montreal, wrote in a study published online in Pediatric Rheumatology.

In the first published analysis of its kind, the researchers conducted a systematic chart review of 100 patients with JIA who attended their final JIA clinic appointment at Montreal Children's Hospital between 1992 and 2005 when they were aged 17 years or older. More than two-thirds of the patients (68%) were female, and the mean age of disease onset was 9.84 years (Pediatr. Rheumatol. 2010 Jan. 11 [doi:10.1186/1546-0096-8-2]).

“Once the name of the adult rheumatologist was identified in the transfer letter, or the last clinic note, his/her office was contacted for permission for a chart review to be conducted,” the researchers explained. The chart was then reviewed for 2 years after transfer.

A patient was deemed to have had an unsuccessful transfer if he or she “never made contact with the identified adult rheumatologist or was lost to follow-up at 2 years following transfer.”

Dr. Hazel and her associates also compared a number of factors among patients who did and did not have successful transfers, including sex, category of JIA, age at diagnosis, use of disease-modifying antirheumatic agents, active joint count, and level of educational attainment.

Of the 100 patients, 52 (52%) met the criteria for unsuccessful transfer from pediatric to adult care. Of these, 17 (33%) did not make initial contact with the appointed adult rheumatologist and 35 (67%) were lost to follow-up at 2 years.

“I was very surprised that more than half of the patients were lost to follow-up,” Dr. Hazel commented in an interview.

Of the patient factors tested, only one was significantly associated with unsuccessful patient transfer: an active joint count of zero at the last visit (odds ratio, 2.67). “This group of young adults with relatively inactive disease should be educated about the importance of ongoing follow-up in the adult milieu given the high possibility of active disease into adulthood,” the researchers advised.

Male sex trended toward a higher risk for unsuccessful transfer (OR, 2.15).

In her interview, Dr. Hazel acknowledged certain limitations of the study, including its retrospective cohort design. “This was a chart review, so we were limited by the information recorded in the charts,” she said.

“We could not track patients who sought out other rheumatologists on their own if they did not request a transfer letter from the pediatric group. While this may have improved the rate of transfer, these cases would still represent a suboptimal situation, with the adult rheumatologist not having information about the pediatric course of illness.”

PHILADELPHIA — Weight loss was linked to significant drops in serum uric acid levels in a prospective study with more than 12,000 men with high cardiovascular risk.

“Weight loss could substantially help achieve a widely accepted therapeutic uric acid target level of 6 mg/dL among men with a high cardiovascular risk profile,” Yanyan Zhu said at the annual meeting of the American College of Rheumatology.

Ms. Zhu and her associates used data from 12,510 men with a high cardiovascular risk profile enrolled in the MRFIT (Multiple Risk Factor Intervention Trial), a study begun in the early 1970s. MRFIT assessed the role of multiple risk-factor interventions, including a special diet, on mortality from coronary heart disease.

The men's mean age at baseline was 46 years. Their average body mass index was 28 kg/m

The study design had the men return annually for clinical assessments for 6 years. During follow-up, 39% had weight loss, 31% had no weight change, and 30% gained weight.

In an analysis that adjusted for baseline covariables of hypertension, diuretic use, alcohol use, and serum creatinine, men who lost weight during follow-up had a statistically significant reduction in their risk for having hyperuricemia, said Ms. Zhu, an epidemiologist at Boston University. The more weight they lost, the lower their risk for hyperuricemia. (See box.) A weight loss of at least 10 kg was associated with a 56% drop in the risk for hyperuricemia. In contrast, men who gained weight during follow-up had a significantly increased risk for hyperuricemia. Again, the risk rose with greater weight gain, with a weight gain of at least 10 kg associated with a 54% increased risk for hyperuricemia

A second analysis showed similar, significant relationships between changes in weight and changes in the serum level of uric acid. The more weight patients lost, the lower their uric acid levels fell, whereas the more weight they gained, the higher their levels rose. (See box.)

Ms. Zhu and her associates hypothesized that the impact of weight change on serum uric acid occurred through changes in uric acid production and renal excretion.

Ms. Zhu had no disclosures.

Source Elsevier Global Medical News

PHILADELPHIA — Weight loss was linked to significant drops in serum uric acid levels in a prospective study with more than 12,000 men with high cardiovascular risk.

“Weight loss could substantially help achieve a widely accepted therapeutic uric acid target level of 6 mg/dL among men with a high cardiovascular risk profile,” Yanyan Zhu said at the annual meeting of the American College of Rheumatology.

Ms. Zhu and her associates used data from 12,510 men with a high cardiovascular risk profile enrolled in the MRFIT (Multiple Risk Factor Intervention Trial), a study begun in the early 1970s. MRFIT assessed the role of multiple risk-factor interventions, including a special diet, on mortality from coronary heart disease.

The men's mean age at baseline was 46 years. Their average body mass index was 28 kg/m

The study design had the men return annually for clinical assessments for 6 years. During follow-up, 39% had weight loss, 31% had no weight change, and 30% gained weight.

In an analysis that adjusted for baseline covariables of hypertension, diuretic use, alcohol use, and serum creatinine, men who lost weight during follow-up had a statistically significant reduction in their risk for having hyperuricemia, said Ms. Zhu, an epidemiologist at Boston University. The more weight they lost, the lower their risk for hyperuricemia. (See box.) A weight loss of at least 10 kg was associated with a 56% drop in the risk for hyperuricemia. In contrast, men who gained weight during follow-up had a significantly increased risk for hyperuricemia. Again, the risk rose with greater weight gain, with a weight gain of at least 10 kg associated with a 54% increased risk for hyperuricemia

A second analysis showed similar, significant relationships between changes in weight and changes in the serum level of uric acid. The more weight patients lost, the lower their uric acid levels fell, whereas the more weight they gained, the higher their levels rose. (See box.)

Ms. Zhu and her associates hypothesized that the impact of weight change on serum uric acid occurred through changes in uric acid production and renal excretion.

Ms. Zhu had no disclosures.

Source Elsevier Global Medical News

PHILADELPHIA — Weight loss was linked to significant drops in serum uric acid levels in a prospective study with more than 12,000 men with high cardiovascular risk.

“Weight loss could substantially help achieve a widely accepted therapeutic uric acid target level of 6 mg/dL among men with a high cardiovascular risk profile,” Yanyan Zhu said at the annual meeting of the American College of Rheumatology.

Ms. Zhu and her associates used data from 12,510 men with a high cardiovascular risk profile enrolled in the MRFIT (Multiple Risk Factor Intervention Trial), a study begun in the early 1970s. MRFIT assessed the role of multiple risk-factor interventions, including a special diet, on mortality from coronary heart disease.

The men's mean age at baseline was 46 years. Their average body mass index was 28 kg/m

The study design had the men return annually for clinical assessments for 6 years. During follow-up, 39% had weight loss, 31% had no weight change, and 30% gained weight.

In an analysis that adjusted for baseline covariables of hypertension, diuretic use, alcohol use, and serum creatinine, men who lost weight during follow-up had a statistically significant reduction in their risk for having hyperuricemia, said Ms. Zhu, an epidemiologist at Boston University. The more weight they lost, the lower their risk for hyperuricemia. (See box.) A weight loss of at least 10 kg was associated with a 56% drop in the risk for hyperuricemia. In contrast, men who gained weight during follow-up had a significantly increased risk for hyperuricemia. Again, the risk rose with greater weight gain, with a weight gain of at least 10 kg associated with a 54% increased risk for hyperuricemia

A second analysis showed similar, significant relationships between changes in weight and changes in the serum level of uric acid. The more weight patients lost, the lower their uric acid levels fell, whereas the more weight they gained, the higher their levels rose. (See box.)

Ms. Zhu and her associates hypothesized that the impact of weight change on serum uric acid occurred through changes in uric acid production and renal excretion.

Ms. Zhu had no disclosures.

Source Elsevier Global Medical News

The monoclonal antibody tocilizumab has received approval by the U.S. Food and Drug Administration for the treatment of moderate to severely active rheumatoid arthritis in adult patients who have failed one or more tumor necrosis factor blockers, according to an announcement made Jan. 11 by the drug's manufacturer, Roche Holding AG.

Tocilizumab (Actemra) is the first interleukin-6 (IL-6) receptor inhibitor to be approved for the treatment of RA, and it can be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs), according to the statement. The drug was codeveloped by Chugai Pharmaceutical Co. and its parent company, Roche.

The approval comes on the heels of an extensive clinical development program comprising five phase III trials, as well as a resubmission of documents, including a proposal for a risk evaluation and mitigation strategy. The pivotal clinical trials include RADIATE (Research on Actemra Determining Efficacy after Anti-TNF Failures), OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders), TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy), AMBITION (Actemra vs. Methotrexate Double-Blind Investigative Trial in Monotherapy), and LITHE (Tocilizumab Safety and the Prevention of Structural Joint Damage).

In the RADIATE trial, 30% of patients who received tocilizumab in combination with methotrexate achieved disease remission, compared with 1.6% of patients receiving methotrexate alone. Lead investigator Dr. Paul Emery, professor of rheumatology at the University of Leeds (England), and colleagues wrote that the findings were especially promising for that subset of RA patients who have failed to achieve adequate symptom relief with anti-TNF agents (Ann. Rheum. Dis. 2008;67:1516–23).

The results from the OPTION trial showed that 59% of the patients with RA who had incomplete responses to methotrexate achieved an ACR 20 response following treatment with tocilizumab 8 mg/kg, compared with 26% of patients treated with placebo, and 27% of the patients on tocilizumab achieved remission, compared with 0.8% in the placebo group (Lancet 2008;371:987–97).

Similarly, in the TOWARD trial, 61% of patients who received tocilizumab in a dose of 8 mg/kg achieved an ACR 20 response at 24 weeks, compared with 25% of patients treated with placebo plus DMARDs, and approximately 38% of tocilizumab-treated patients met ACR 50 criteria for symptom improvement, compared with 9% of patients receiving placebo (Arthritis Rheum. 2008;58:2968–80).

The AMBITION study, in which 70% of patients who received a dose of 8 mg/kg achieved an ACR 20 response at 24 weeks, was the first to show that treatment with a single biologic agent was superior to methotrexate alone for the treatment of RA at 6 months, according to a press release issued by Roche when the phase III results were released in 2008 at the annual Congress of the European League Against Rheumatism.

Findings from the LITHE study, which were presented by lead investigator Dr. Roy M. Fleischmann of the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas, at the 2009 annual meeting of the American College of Rheumatology, showed that over a 2-year period, there was no radiographic progression or joint damage in 75% of RA patients taking tocilizumab 4 mg/kg plus methotrexate, or in 85% of those taking tocilizumab 8 mg/kg and methotrexate, compared with 66% of patients taking methotrexate alone.

Among the serious tocilizumab-related adverse events that have been reported in the clinical trials are infections (including tuberculosis) that led to hospitalization or death, and bacterial, invasive fungal, viral, and other infections; gastrointestinal perforations; hypersensitivity reactions; and cellulitis.

Some of the common side effects included upper respiratory infections, including pneumonia; inflammation of the nose and throat; headache; high blood pressure; increased liver enzymes; increased cholesterol levels; neutrophil decreases; and platelet decreases, according to the press release.

Tocilizumab is expected to become available in the United States soon.

My Take

Insurance Coverage May Be an Issue

Rheumatologists have been hearing a lot of preapproval hype about this agent from Roche.

Our interest is piqued by the novelty of the mechanism of action of tocilizumab. There are multiple anti-TNF medications currently, and their manufacturers are trying hard to convince clinicians to choose one medication over another, even though they are probably more similar than different. As an IL-6 blocker, tocilizumab is different.

The new-drug hype notwithstanding, there are still a number of questions to be answered before clinicians can consider the potential clinical impact of tocilizumab. The main questions for me are: Is this medication any safer or more dangerous than the current biologic drugs? Is this medication more or less affordable, or accessible, than the current biologics? Where does this medication belong in the treatment algorithm?

Undoubtedly, the company is going to try to convince doctors to use this medication immediately after methotrexate failure, but they will first have to convince doctors, and insurers, that this strategy is warranted.

LARRY GREENBAUM, M.D., is a private practice rheumatologist in Indianapolis. He has no financial disclosures to make that are relevant to the approval of tocilizumab.

The monoclonal antibody tocilizumab has received approval by the U.S. Food and Drug Administration for the treatment of moderate to severely active rheumatoid arthritis in adult patients who have failed one or more tumor necrosis factor blockers, according to an announcement made Jan. 11 by the drug's manufacturer, Roche Holding AG.

Tocilizumab (Actemra) is the first interleukin-6 (IL-6) receptor inhibitor to be approved for the treatment of RA, and it can be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs), according to the statement. The drug was codeveloped by Chugai Pharmaceutical Co. and its parent company, Roche.

The approval comes on the heels of an extensive clinical development program comprising five phase III trials, as well as a resubmission of documents, including a proposal for a risk evaluation and mitigation strategy. The pivotal clinical trials include RADIATE (Research on Actemra Determining Efficacy after Anti-TNF Failures), OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders), TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy), AMBITION (Actemra vs. Methotrexate Double-Blind Investigative Trial in Monotherapy), and LITHE (Tocilizumab Safety and the Prevention of Structural Joint Damage).

In the RADIATE trial, 30% of patients who received tocilizumab in combination with methotrexate achieved disease remission, compared with 1.6% of patients receiving methotrexate alone. Lead investigator Dr. Paul Emery, professor of rheumatology at the University of Leeds (England), and colleagues wrote that the findings were especially promising for that subset of RA patients who have failed to achieve adequate symptom relief with anti-TNF agents (Ann. Rheum. Dis. 2008;67:1516–23).

The results from the OPTION trial showed that 59% of the patients with RA who had incomplete responses to methotrexate achieved an ACR 20 response following treatment with tocilizumab 8 mg/kg, compared with 26% of patients treated with placebo, and 27% of the patients on tocilizumab achieved remission, compared with 0.8% in the placebo group (Lancet 2008;371:987–97).

Similarly, in the TOWARD trial, 61% of patients who received tocilizumab in a dose of 8 mg/kg achieved an ACR 20 response at 24 weeks, compared with 25% of patients treated with placebo plus DMARDs, and approximately 38% of tocilizumab-treated patients met ACR 50 criteria for symptom improvement, compared with 9% of patients receiving placebo (Arthritis Rheum. 2008;58:2968–80).

The AMBITION study, in which 70% of patients who received a dose of 8 mg/kg achieved an ACR 20 response at 24 weeks, was the first to show that treatment with a single biologic agent was superior to methotrexate alone for the treatment of RA at 6 months, according to a press release issued by Roche when the phase III results were released in 2008 at the annual Congress of the European League Against Rheumatism.

Findings from the LITHE study, which were presented by lead investigator Dr. Roy M. Fleischmann of the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas, at the 2009 annual meeting of the American College of Rheumatology, showed that over a 2-year period, there was no radiographic progression or joint damage in 75% of RA patients taking tocilizumab 4 mg/kg plus methotrexate, or in 85% of those taking tocilizumab 8 mg/kg and methotrexate, compared with 66% of patients taking methotrexate alone.

Among the serious tocilizumab-related adverse events that have been reported in the clinical trials are infections (including tuberculosis) that led to hospitalization or death, and bacterial, invasive fungal, viral, and other infections; gastrointestinal perforations; hypersensitivity reactions; and cellulitis.

Some of the common side effects included upper respiratory infections, including pneumonia; inflammation of the nose and throat; headache; high blood pressure; increased liver enzymes; increased cholesterol levels; neutrophil decreases; and platelet decreases, according to the press release.

Tocilizumab is expected to become available in the United States soon.

My Take

Insurance Coverage May Be an Issue

Rheumatologists have been hearing a lot of preapproval hype about this agent from Roche.

Our interest is piqued by the novelty of the mechanism of action of tocilizumab. There are multiple anti-TNF medications currently, and their manufacturers are trying hard to convince clinicians to choose one medication over another, even though they are probably more similar than different. As an IL-6 blocker, tocilizumab is different.

The new-drug hype notwithstanding, there are still a number of questions to be answered before clinicians can consider the potential clinical impact of tocilizumab. The main questions for me are: Is this medication any safer or more dangerous than the current biologic drugs? Is this medication more or less affordable, or accessible, than the current biologics? Where does this medication belong in the treatment algorithm?

Undoubtedly, the company is going to try to convince doctors to use this medication immediately after methotrexate failure, but they will first have to convince doctors, and insurers, that this strategy is warranted.

LARRY GREENBAUM, M.D., is a private practice rheumatologist in Indianapolis. He has no financial disclosures to make that are relevant to the approval of tocilizumab.

The monoclonal antibody tocilizumab has received approval by the U.S. Food and Drug Administration for the treatment of moderate to severely active rheumatoid arthritis in adult patients who have failed one or more tumor necrosis factor blockers, according to an announcement made Jan. 11 by the drug's manufacturer, Roche Holding AG.

Tocilizumab (Actemra) is the first interleukin-6 (IL-6) receptor inhibitor to be approved for the treatment of RA, and it can be used alone or in combination with methotrexate or other disease-modifying antirheumatic drugs (DMARDs), according to the statement. The drug was codeveloped by Chugai Pharmaceutical Co. and its parent company, Roche.

The approval comes on the heels of an extensive clinical development program comprising five phase III trials, as well as a resubmission of documents, including a proposal for a risk evaluation and mitigation strategy. The pivotal clinical trials include RADIATE (Research on Actemra Determining Efficacy after Anti-TNF Failures), OPTION (Tocilizumab Pivotal Trial in Methotrexate Inadequate Responders), TOWARD (Tocilizumab in Combination With Traditional DMARD Therapy), AMBITION (Actemra vs. Methotrexate Double-Blind Investigative Trial in Monotherapy), and LITHE (Tocilizumab Safety and the Prevention of Structural Joint Damage).

In the RADIATE trial, 30% of patients who received tocilizumab in combination with methotrexate achieved disease remission, compared with 1.6% of patients receiving methotrexate alone. Lead investigator Dr. Paul Emery, professor of rheumatology at the University of Leeds (England), and colleagues wrote that the findings were especially promising for that subset of RA patients who have failed to achieve adequate symptom relief with anti-TNF agents (Ann. Rheum. Dis. 2008;67:1516–23).

The results from the OPTION trial showed that 59% of the patients with RA who had incomplete responses to methotrexate achieved an ACR 20 response following treatment with tocilizumab 8 mg/kg, compared with 26% of patients treated with placebo, and 27% of the patients on tocilizumab achieved remission, compared with 0.8% in the placebo group (Lancet 2008;371:987–97).

Similarly, in the TOWARD trial, 61% of patients who received tocilizumab in a dose of 8 mg/kg achieved an ACR 20 response at 24 weeks, compared with 25% of patients treated with placebo plus DMARDs, and approximately 38% of tocilizumab-treated patients met ACR 50 criteria for symptom improvement, compared with 9% of patients receiving placebo (Arthritis Rheum. 2008;58:2968–80).

The AMBITION study, in which 70% of patients who received a dose of 8 mg/kg achieved an ACR 20 response at 24 weeks, was the first to show that treatment with a single biologic agent was superior to methotrexate alone for the treatment of RA at 6 months, according to a press release issued by Roche when the phase III results were released in 2008 at the annual Congress of the European League Against Rheumatism.

Findings from the LITHE study, which were presented by lead investigator Dr. Roy M. Fleischmann of the department of internal medicine at the University of Texas Southwestern Medical Center, Dallas, at the 2009 annual meeting of the American College of Rheumatology, showed that over a 2-year period, there was no radiographic progression or joint damage in 75% of RA patients taking tocilizumab 4 mg/kg plus methotrexate, or in 85% of those taking tocilizumab 8 mg/kg and methotrexate, compared with 66% of patients taking methotrexate alone.

Among the serious tocilizumab-related adverse events that have been reported in the clinical trials are infections (including tuberculosis) that led to hospitalization or death, and bacterial, invasive fungal, viral, and other infections; gastrointestinal perforations; hypersensitivity reactions; and cellulitis.

Some of the common side effects included upper respiratory infections, including pneumonia; inflammation of the nose and throat; headache; high blood pressure; increased liver enzymes; increased cholesterol levels; neutrophil decreases; and platelet decreases, according to the press release.

Tocilizumab is expected to become available in the United States soon.

My Take

Insurance Coverage May Be an Issue

Rheumatologists have been hearing a lot of preapproval hype about this agent from Roche.

Our interest is piqued by the novelty of the mechanism of action of tocilizumab. There are multiple anti-TNF medications currently, and their manufacturers are trying hard to convince clinicians to choose one medication over another, even though they are probably more similar than different. As an IL-6 blocker, tocilizumab is different.

The new-drug hype notwithstanding, there are still a number of questions to be answered before clinicians can consider the potential clinical impact of tocilizumab. The main questions for me are: Is this medication any safer or more dangerous than the current biologic drugs? Is this medication more or less affordable, or accessible, than the current biologics? Where does this medication belong in the treatment algorithm?

Undoubtedly, the company is going to try to convince doctors to use this medication immediately after methotrexate failure, but they will first have to convince doctors, and insurers, that this strategy is warranted.

LARRY GREENBAUM, M.D., is a private practice rheumatologist in Indianapolis. He has no financial disclosures to make that are relevant to the approval of tocilizumab.

NEW YORK — The soft data that can be gathered from self-administered patient questionnaires are more telling about how a patient with rheumatoid arthritis is faring than are x-rays or some lab tests that are wrongly considered to be prognostic.

Dr. Theodore Pincus recently told a group of rheumatologists at a course sponsored by New York University that “patient questionnaire scores are the most valuable data we collect in taking care of patients.”

“The rheumatologist should be leading the world in recognizing these matters, rather than trying to say that we can be like cardiologists and look at images,” said Dr. Pincus of the department of medicine at the university.

That's why he encourages physicians to make patient questionnaires a standard part of the assessment of RA patients and then document those numerical measurements for easy reference.

Questionnaires like the Routine Assessment of Patient Index Data 3 (RAPID3) can be administered cheaply—for just the cost of pencils and photocopies—and scored by physicians in 5–10 seconds, he said.

These types of patient-oriented measures are especially important in rheumatology where there is no single standard measure when it comes to diagnosis or predicting functionality, said Dr. Pincus.

Functional disability, patient global estimate, socioeconomic status, and age are better predictors of cost, work disability, and death in RA than are rheumatoid factor and radiographs, he noted.

Although the conventional measures that make up the American College of Rheumatology core data set have served the specialty well, they all have their limitations, said Dr. Pincus.

Joint counts are the most specific measure to assess patients with RA, but the measure is not necessarily the most significant when it comes to prognosis and management, he said. Joint counts may improve over time, even while joint damage and functional disability continue to progress.

It also takes physicians significantly longer to perform a joint count than to score a patient self-assessment (about 1.5 minutes vs. about 5–10 seconds).

And many rheumatologists don't actually perform formal tender and swollen joint counts on the patients they examine, he said.

Radiographs also have drawbacks, Dr. Pincus said. Although clinical trials have shown statistically significant data from radiographs, it's still unclear how important they are clinically in individual patients, he said.

The usefulness of x-rays is also limited because treatment is often initiated prior to the emergence of erosions.

Laboratory tests, which are often seen by physicians and patients as the most important measures, also fall short in rheumatology. For example, medical textbooks have said for years that the erythrocyte sedimentation rate is increased in nearly all patients with active RA, but today the data show that many patients with active RA do not have an increased ESR, Dr. Pincus said.

Studies from around the world have shown that as many as 37%–45% of RA patients have an ESR value less than 28 mm/hour, which is within normal limits (J. Rheumatol. 1994;21:1227–37).

While a complete blood count test is often of great value, generally laboratory tests tend to be overrated in rheumatology, he said.

Disclosures: Dr. Pincus disclosed a financial relationship with a number of pharmaceutical companies including Amgen Inc., Bristol-Myers Squibb Co., Abbott Laboratories, Wyeth Pharmaceuticals, Genentech, and UCB.

Rheumatologists should be leading the way in recognizing the validity of patient-completed questionnaires.

Source DR. PINCUS

NEW YORK — The soft data that can be gathered from self-administered patient questionnaires are more telling about how a patient with rheumatoid arthritis is faring than are x-rays or some lab tests that are wrongly considered to be prognostic.

Dr. Theodore Pincus recently told a group of rheumatologists at a course sponsored by New York University that “patient questionnaire scores are the most valuable data we collect in taking care of patients.”

“The rheumatologist should be leading the world in recognizing these matters, rather than trying to say that we can be like cardiologists and look at images,” said Dr. Pincus of the department of medicine at the university.

That's why he encourages physicians to make patient questionnaires a standard part of the assessment of RA patients and then document those numerical measurements for easy reference.

Questionnaires like the Routine Assessment of Patient Index Data 3 (RAPID3) can be administered cheaply—for just the cost of pencils and photocopies—and scored by physicians in 5–10 seconds, he said.

These types of patient-oriented measures are especially important in rheumatology where there is no single standard measure when it comes to diagnosis or predicting functionality, said Dr. Pincus.

Functional disability, patient global estimate, socioeconomic status, and age are better predictors of cost, work disability, and death in RA than are rheumatoid factor and radiographs, he noted.

Although the conventional measures that make up the American College of Rheumatology core data set have served the specialty well, they all have their limitations, said Dr. Pincus.

Joint counts are the most specific measure to assess patients with RA, but the measure is not necessarily the most significant when it comes to prognosis and management, he said. Joint counts may improve over time, even while joint damage and functional disability continue to progress.

It also takes physicians significantly longer to perform a joint count than to score a patient self-assessment (about 1.5 minutes vs. about 5–10 seconds).

And many rheumatologists don't actually perform formal tender and swollen joint counts on the patients they examine, he said.

Radiographs also have drawbacks, Dr. Pincus said. Although clinical trials have shown statistically significant data from radiographs, it's still unclear how important they are clinically in individual patients, he said.

The usefulness of x-rays is also limited because treatment is often initiated prior to the emergence of erosions.

Laboratory tests, which are often seen by physicians and patients as the most important measures, also fall short in rheumatology. For example, medical textbooks have said for years that the erythrocyte sedimentation rate is increased in nearly all patients with active RA, but today the data show that many patients with active RA do not have an increased ESR, Dr. Pincus said.

Studies from around the world have shown that as many as 37%–45% of RA patients have an ESR value less than 28 mm/hour, which is within normal limits (J. Rheumatol. 1994;21:1227–37).

While a complete blood count test is often of great value, generally laboratory tests tend to be overrated in rheumatology, he said.

Disclosures: Dr. Pincus disclosed a financial relationship with a number of pharmaceutical companies including Amgen Inc., Bristol-Myers Squibb Co., Abbott Laboratories, Wyeth Pharmaceuticals, Genentech, and UCB.

Rheumatologists should be leading the way in recognizing the validity of patient-completed questionnaires.

Source DR. PINCUS

NEW YORK — The soft data that can be gathered from self-administered patient questionnaires are more telling about how a patient with rheumatoid arthritis is faring than are x-rays or some lab tests that are wrongly considered to be prognostic.

Dr. Theodore Pincus recently told a group of rheumatologists at a course sponsored by New York University that “patient questionnaire scores are the most valuable data we collect in taking care of patients.”

“The rheumatologist should be leading the world in recognizing these matters, rather than trying to say that we can be like cardiologists and look at images,” said Dr. Pincus of the department of medicine at the university.

That's why he encourages physicians to make patient questionnaires a standard part of the assessment of RA patients and then document those numerical measurements for easy reference.

Questionnaires like the Routine Assessment of Patient Index Data 3 (RAPID3) can be administered cheaply—for just the cost of pencils and photocopies—and scored by physicians in 5–10 seconds, he said.

These types of patient-oriented measures are especially important in rheumatology where there is no single standard measure when it comes to diagnosis or predicting functionality, said Dr. Pincus.

Functional disability, patient global estimate, socioeconomic status, and age are better predictors of cost, work disability, and death in RA than are rheumatoid factor and radiographs, he noted.

Although the conventional measures that make up the American College of Rheumatology core data set have served the specialty well, they all have their limitations, said Dr. Pincus.

Joint counts are the most specific measure to assess patients with RA, but the measure is not necessarily the most significant when it comes to prognosis and management, he said. Joint counts may improve over time, even while joint damage and functional disability continue to progress.

It also takes physicians significantly longer to perform a joint count than to score a patient self-assessment (about 1.5 minutes vs. about 5–10 seconds).

And many rheumatologists don't actually perform formal tender and swollen joint counts on the patients they examine, he said.

Radiographs also have drawbacks, Dr. Pincus said. Although clinical trials have shown statistically significant data from radiographs, it's still unclear how important they are clinically in individual patients, he said.

The usefulness of x-rays is also limited because treatment is often initiated prior to the emergence of erosions.

Laboratory tests, which are often seen by physicians and patients as the most important measures, also fall short in rheumatology. For example, medical textbooks have said for years that the erythrocyte sedimentation rate is increased in nearly all patients with active RA, but today the data show that many patients with active RA do not have an increased ESR, Dr. Pincus said.

Studies from around the world have shown that as many as 37%–45% of RA patients have an ESR value less than 28 mm/hour, which is within normal limits (J. Rheumatol. 1994;21:1227–37).

While a complete blood count test is often of great value, generally laboratory tests tend to be overrated in rheumatology, he said.

Disclosures: Dr. Pincus disclosed a financial relationship with a number of pharmaceutical companies including Amgen Inc., Bristol-Myers Squibb Co., Abbott Laboratories, Wyeth Pharmaceuticals, Genentech, and UCB.

Rheumatologists should be leading the way in recognizing the validity of patient-completed questionnaires.

Source DR. PINCUS

NEW YORK — Building on the work in developing a clinical definition of remission in rheumatoid arthritis, a group of clinicians and researchers is interested in creating a complementary patient term called “absence of disease.”

Rheumatologists from around the world will begin discussing how to develop this patient-centered definition in Malaysian Borneo in May at the next meeting of OMERACT (Outcome Measures in Rheumatology), an international network aimed at improving outcomes assessment in rheumatology.

It's important to ask patients for their view of what “absence of disease” means, because they see “remission” so differently from the way physicians do, Dr. Maarten Boers, a member of the OMERACT executive committee, said at a rheumatology course sponsored by New York University. The current remission term is a classic physician-centric definition that is largely based on inflammation, he said.

“If you talk to patients, they talk about totally different things than we talk about in terms of disease,” Dr. Boers, a professor at VU University Medical Center in Amsterdam, said in an interview.

Although patients were involved in developing the remission definition by OMERACT, that dimension wasn's fully studied. This time around, the organization plans to spend about 2 years performing qualitative work. They won's have to start from scratch, though, Dr. Boers said, because there has already been qualitative work done on a related issue: the impact of disease, which could be interpreted as the opposite of the “absence of disease” concept.

Disclosures: Dr. Boers said he had no relevant financial disclosures to make.

NEW YORK — Building on the work in developing a clinical definition of remission in rheumatoid arthritis, a group of clinicians and researchers is interested in creating a complementary patient term called “absence of disease.”

Rheumatologists from around the world will begin discussing how to develop this patient-centered definition in Malaysian Borneo in May at the next meeting of OMERACT (Outcome Measures in Rheumatology), an international network aimed at improving outcomes assessment in rheumatology.

It's important to ask patients for their view of what “absence of disease” means, because they see “remission” so differently from the way physicians do, Dr. Maarten Boers, a member of the OMERACT executive committee, said at a rheumatology course sponsored by New York University. The current remission term is a classic physician-centric definition that is largely based on inflammation, he said.

“If you talk to patients, they talk about totally different things than we talk about in terms of disease,” Dr. Boers, a professor at VU University Medical Center in Amsterdam, said in an interview.

Although patients were involved in developing the remission definition by OMERACT, that dimension wasn's fully studied. This time around, the organization plans to spend about 2 years performing qualitative work. They won's have to start from scratch, though, Dr. Boers said, because there has already been qualitative work done on a related issue: the impact of disease, which could be interpreted as the opposite of the “absence of disease” concept.

Disclosures: Dr. Boers said he had no relevant financial disclosures to make.

NEW YORK — Building on the work in developing a clinical definition of remission in rheumatoid arthritis, a group of clinicians and researchers is interested in creating a complementary patient term called “absence of disease.”

Rheumatologists from around the world will begin discussing how to develop this patient-centered definition in Malaysian Borneo in May at the next meeting of OMERACT (Outcome Measures in Rheumatology), an international network aimed at improving outcomes assessment in rheumatology.

It's important to ask patients for their view of what “absence of disease” means, because they see “remission” so differently from the way physicians do, Dr. Maarten Boers, a member of the OMERACT executive committee, said at a rheumatology course sponsored by New York University. The current remission term is a classic physician-centric definition that is largely based on inflammation, he said.

“If you talk to patients, they talk about totally different things than we talk about in terms of disease,” Dr. Boers, a professor at VU University Medical Center in Amsterdam, said in an interview.

Although patients were involved in developing the remission definition by OMERACT, that dimension wasn's fully studied. This time around, the organization plans to spend about 2 years performing qualitative work. They won's have to start from scratch, though, Dr. Boers said, because there has already been qualitative work done on a related issue: the impact of disease, which could be interpreted as the opposite of the “absence of disease” concept.

Disclosures: Dr. Boers said he had no relevant financial disclosures to make.

The timing of influenza and pneumococcal vaccinations can substantially influence the degree of antibody response in rheumatoid arthritis patients taking rituximab, concluded investigators in two independent studies.

Rituximab, which acts by depleting B cells, also reduces patients' humoral and cellular immune responses, they said.

In one of the two studies reported in Arthritis & Rheumatism, Dr. Sander van Assen of the University Medical Center Groningen (the Netherlands) and colleagues investigated the efficacy of influenza vaccination in RA patients who are treated with rituximab. They also assessed the duration of the possible suppression of the humoral immune response following rituximab treatment, and observed a decreased humoral response following vaccination that was modestly restored 6–10 months after rituximab administration (Arthritis Rheum., 2010;62:75–81).

The study comprised two groups of RA patients—a rituximab group and a methotrexate group—and one group of 29 healthy controls. The rituximab group consisted of 23 patients, 22 of whom received two cycles of 1,000 mg of the biologic with 100 mg intravenous methylprednisolone, and 1 patient with mixed cryoglobulinemia who received four cycles of 375 mg/m

Immediately before and a mean 28 days after vaccination, blood was drawn from all patients to measure CD19+ cell counts, C-reactive protein levels, erythrocyte sedimentation rates, and anti-influenza antibodies. Compared with baseline measures, geometric mean titres (GMTs) for all three influenza strains tested (A[H3N2], A[H1N1], and B) increased significantly in the healthy controls and the methotrexate group, but not in the rituximab group as a whole, the authors reported. In the late rituximab subgroup, a rise was noted in the GMTs for the A(H3N2) and A(H1N1) flu strains, “indicating some recovery of the humoral immune response 6–10 months after treatment with rituximab,” they wrote.

With respect to CD19+ cell counts, the baseline measures for both the early and late rituximab subgroups were comparable. At 28 days after vaccination, however, significantly more B cells were present in the late vs. early group, according to the authors.

Seroconversion and seroprotection occurred less often in the rituximab group than in the methotrexate-treated group for both influenza A strains. Seroprotection occurred less often in the rituximab group than in the healthy controls for the A(H1N1) strains, the authors wrote. Of the three cases of seroconversion and six cases of seroprotection observed in the rituximab group, all but one of the seroprotection cases occurred in the late rituximab subgroup, they stated.

An examination of vaccination safety showed no differences among the three groups regarding the occurrence of side effects, the authors wrote. Also, disease activity in the methotrexate and rituximab groups, assessed with the DAS28 prior to and 7 and 28 days after vaccination, was not influenced by vaccination.

Because patients who were treated with rituximab appear to have a “severely hampered” humoral immune response to the trivalent subunit influenza vaccination, preemptive influenza vaccination should be considered prior to rituximab administration, the authors wrote, noting the importance of yearly influenza vaccination, given the increase in anti-influenza titers observed in previously vaccinated patients.

In the second study, a controlled trial by Dr. Clifton O. Bingham III of Johns Hopkins University, Baltimore, and colleagues, the investigators examined the immunization responses (humoral immunity and the cellular immune response) of rituximab-treated RA patients who received tetanus toxoid, 23-valent pneumococcal polysaccharide (PPV23), and keyhole limpet hemocyanin (KLH) vaccines, and they evaluated the effects of rituximab-induced CD20+ B-cell depletion on immune responses to these vaccinations (Arthritis Rheum. 2010;62:62–74).

The study enrolled 103 patients aged 18–65 years who had active RA and were receiving a stable dosage of 10–25 mg/wk of methotrexate from 26 U.S. centers between January 2006 and December 2007. Patients were stratified by site and age (18–50 years and 51–65 years) and then were randomized in a 2:1 manner to receive either two cycles of 1,000 mg rituximab (open label) 2 weeks apart plus a stable dose of methotrexate (68 patients), or methotrexate alone (32 patients). In the rituximab-plus-methotrexate group, 100 mg of methylprednisolone was administered intravenously before each rituximab infusion, the authors wrote.

Patients in both groups received the tetanus toxoid adsorbed vaccine, PPV23, KLH, and a Candida albicans skin test according to the protocol schedule. Antitetanus, antipneumonococcal, and anti-KLH serum IgG levels were measured prior to and 4 weeks following each respective vaccine administration, and the delayed-type hypersensitivity (DTH) skin test response was measured 2–3 days following placement, the authors wrote.

An analysis of the results showed that patients in both groups responded similarly to tetanus toxoid vaccine, with 25 patients in the rituximab group (39%) and 11 patients in the methotrexate-only group (42%) showing a more than fourfold risk in antitetanus IgG titer, and 35 rituximab patients and 16 methotrexate patients demonstrating a more than twofold rise, the authors reported. Similarly, they wrote, “the ability to maintain a positive DTH response to the C. albicans skin test was comparable in both groups,” confirming that rituximab had no incremental effect on the patients'ability to mount a DTH response.

Significant differences were observed in the responses to PPV23 between the two groups, with only 57% of patients in the rituximab group demonstrating a twofold rise in titer in response to one or more serotypes, compared with 82% of the methotrexate-only patients, the authors reported. Similarly, only 47% of the rituximab patients had detectable anti-KLH IgG, compared with 93% of the methotrexate-only group, they noted.

“Because neoantigen and polysaccharide responses are B-cell dependent, decreased responses to KLH and [PPV23] are consistent with rituximab's mechanism of action,” the authors observed. “Despite peripheral B-cell depletion, however, responses to the KLH and [PPV23] vaccine were not completely abrogated in the present study,” they wrote, referring to the 47% of rituximab patients who had a quantifiable anti-KLH response and the 57% and 43% of rituximab patients who mounted responses to at least one and two pneumococcal serotypes, respectively. The authors concluded that for maximized vaccination response, “polysaccharide and primary immunizations should be administered prior to rituximab infusions.”

Although both of these studies provide some insight into the effects of rituximab therapy on immune function, “they fall short in offering clues about the causal mechanisms,” Dr. E. William St. Claire of Duke University Medical Center in Durham, N.C., wrote in an editorial (Arthritis Rheum. 2010;62:1–5).

Disclosures: The study reported by Dr. van Assen and colleagues was supported by Roche Nederland and Solvay Pharmaceuticals. The authors reported no additional conflicts of interest. The study reported by Dr. Bingham and colleagues was supported by Genentech Inc. The authors reported having financial relationships with Genentech, Roche, and Merck & Co. One of the authors served on Merck's data and safety monitoring board, and three of the authors own stock or stock options in Genentech. Dr. St. Clair disclosed having financial relationships with Biogen Idec Inc.

The timing of influenza and pneumococcal vaccinations can substantially influence the degree of antibody response in rheumatoid arthritis patients taking rituximab, concluded investigators in two independent studies.

Rituximab, which acts by depleting B cells, also reduces patients' humoral and cellular immune responses, they said.

In one of the two studies reported in Arthritis & Rheumatism, Dr. Sander van Assen of the University Medical Center Groningen (the Netherlands) and colleagues investigated the efficacy of influenza vaccination in RA patients who are treated with rituximab. They also assessed the duration of the possible suppression of the humoral immune response following rituximab treatment, and observed a decreased humoral response following vaccination that was modestly restored 6–10 months after rituximab administration (Arthritis Rheum., 2010;62:75–81).

The study comprised two groups of RA patients—a rituximab group and a methotrexate group—and one group of 29 healthy controls. The rituximab group consisted of 23 patients, 22 of whom received two cycles of 1,000 mg of the biologic with 100 mg intravenous methylprednisolone, and 1 patient with mixed cryoglobulinemia who received four cycles of 375 mg/m

Immediately before and a mean 28 days after vaccination, blood was drawn from all patients to measure CD19+ cell counts, C-reactive protein levels, erythrocyte sedimentation rates, and anti-influenza antibodies. Compared with baseline measures, geometric mean titres (GMTs) for all three influenza strains tested (A[H3N2], A[H1N1], and B) increased significantly in the healthy controls and the methotrexate group, but not in the rituximab group as a whole, the authors reported. In the late rituximab subgroup, a rise was noted in the GMTs for the A(H3N2) and A(H1N1) flu strains, “indicating some recovery of the humoral immune response 6–10 months after treatment with rituximab,” they wrote.

With respect to CD19+ cell counts, the baseline measures for both the early and late rituximab subgroups were comparable. At 28 days after vaccination, however, significantly more B cells were present in the late vs. early group, according to the authors.

Seroconversion and seroprotection occurred less often in the rituximab group than in the methotrexate-treated group for both influenza A strains. Seroprotection occurred less often in the rituximab group than in the healthy controls for the A(H1N1) strains, the authors wrote. Of the three cases of seroconversion and six cases of seroprotection observed in the rituximab group, all but one of the seroprotection cases occurred in the late rituximab subgroup, they stated.

An examination of vaccination safety showed no differences among the three groups regarding the occurrence of side effects, the authors wrote. Also, disease activity in the methotrexate and rituximab groups, assessed with the DAS28 prior to and 7 and 28 days after vaccination, was not influenced by vaccination.

Because patients who were treated with rituximab appear to have a “severely hampered” humoral immune response to the trivalent subunit influenza vaccination, preemptive influenza vaccination should be considered prior to rituximab administration, the authors wrote, noting the importance of yearly influenza vaccination, given the increase in anti-influenza titers observed in previously vaccinated patients.

In the second study, a controlled trial by Dr. Clifton O. Bingham III of Johns Hopkins University, Baltimore, and colleagues, the investigators examined the immunization responses (humoral immunity and the cellular immune response) of rituximab-treated RA patients who received tetanus toxoid, 23-valent pneumococcal polysaccharide (PPV23), and keyhole limpet hemocyanin (KLH) vaccines, and they evaluated the effects of rituximab-induced CD20+ B-cell depletion on immune responses to these vaccinations (Arthritis Rheum. 2010;62:62–74).

The study enrolled 103 patients aged 18–65 years who had active RA and were receiving a stable dosage of 10–25 mg/wk of methotrexate from 26 U.S. centers between January 2006 and December 2007. Patients were stratified by site and age (18–50 years and 51–65 years) and then were randomized in a 2:1 manner to receive either two cycles of 1,000 mg rituximab (open label) 2 weeks apart plus a stable dose of methotrexate (68 patients), or methotrexate alone (32 patients). In the rituximab-plus-methotrexate group, 100 mg of methylprednisolone was administered intravenously before each rituximab infusion, the authors wrote.

Patients in both groups received the tetanus toxoid adsorbed vaccine, PPV23, KLH, and a Candida albicans skin test according to the protocol schedule. Antitetanus, antipneumonococcal, and anti-KLH serum IgG levels were measured prior to and 4 weeks following each respective vaccine administration, and the delayed-type hypersensitivity (DTH) skin test response was measured 2–3 days following placement, the authors wrote.

An analysis of the results showed that patients in both groups responded similarly to tetanus toxoid vaccine, with 25 patients in the rituximab group (39%) and 11 patients in the methotrexate-only group (42%) showing a more than fourfold risk in antitetanus IgG titer, and 35 rituximab patients and 16 methotrexate patients demonstrating a more than twofold rise, the authors reported. Similarly, they wrote, “the ability to maintain a positive DTH response to the C. albicans skin test was comparable in both groups,” confirming that rituximab had no incremental effect on the patients'ability to mount a DTH response.

Significant differences were observed in the responses to PPV23 between the two groups, with only 57% of patients in the rituximab group demonstrating a twofold rise in titer in response to one or more serotypes, compared with 82% of the methotrexate-only patients, the authors reported. Similarly, only 47% of the rituximab patients had detectable anti-KLH IgG, compared with 93% of the methotrexate-only group, they noted.

“Because neoantigen and polysaccharide responses are B-cell dependent, decreased responses to KLH and [PPV23] are consistent with rituximab's mechanism of action,” the authors observed. “Despite peripheral B-cell depletion, however, responses to the KLH and [PPV23] vaccine were not completely abrogated in the present study,” they wrote, referring to the 47% of rituximab patients who had a quantifiable anti-KLH response and the 57% and 43% of rituximab patients who mounted responses to at least one and two pneumococcal serotypes, respectively. The authors concluded that for maximized vaccination response, “polysaccharide and primary immunizations should be administered prior to rituximab infusions.”

Although both of these studies provide some insight into the effects of rituximab therapy on immune function, “they fall short in offering clues about the causal mechanisms,” Dr. E. William St. Claire of Duke University Medical Center in Durham, N.C., wrote in an editorial (Arthritis Rheum. 2010;62:1–5).

Disclosures: The study reported by Dr. van Assen and colleagues was supported by Roche Nederland and Solvay Pharmaceuticals. The authors reported no additional conflicts of interest. The study reported by Dr. Bingham and colleagues was supported by Genentech Inc. The authors reported having financial relationships with Genentech, Roche, and Merck & Co. One of the authors served on Merck's data and safety monitoring board, and three of the authors own stock or stock options in Genentech. Dr. St. Clair disclosed having financial relationships with Biogen Idec Inc.

The timing of influenza and pneumococcal vaccinations can substantially influence the degree of antibody response in rheumatoid arthritis patients taking rituximab, concluded investigators in two independent studies.

Rituximab, which acts by depleting B cells, also reduces patients' humoral and cellular immune responses, they said.

In one of the two studies reported in Arthritis & Rheumatism, Dr. Sander van Assen of the University Medical Center Groningen (the Netherlands) and colleagues investigated the efficacy of influenza vaccination in RA patients who are treated with rituximab. They also assessed the duration of the possible suppression of the humoral immune response following rituximab treatment, and observed a decreased humoral response following vaccination that was modestly restored 6–10 months after rituximab administration (Arthritis Rheum., 2010;62:75–81).

The study comprised two groups of RA patients—a rituximab group and a methotrexate group—and one group of 29 healthy controls. The rituximab group consisted of 23 patients, 22 of whom received two cycles of 1,000 mg of the biologic with 100 mg intravenous methylprednisolone, and 1 patient with mixed cryoglobulinemia who received four cycles of 375 mg/m

Immediately before and a mean 28 days after vaccination, blood was drawn from all patients to measure CD19+ cell counts, C-reactive protein levels, erythrocyte sedimentation rates, and anti-influenza antibodies. Compared with baseline measures, geometric mean titres (GMTs) for all three influenza strains tested (A[H3N2], A[H1N1], and B) increased significantly in the healthy controls and the methotrexate group, but not in the rituximab group as a whole, the authors reported. In the late rituximab subgroup, a rise was noted in the GMTs for the A(H3N2) and A(H1N1) flu strains, “indicating some recovery of the humoral immune response 6–10 months after treatment with rituximab,” they wrote.

With respect to CD19+ cell counts, the baseline measures for both the early and late rituximab subgroups were comparable. At 28 days after vaccination, however, significantly more B cells were present in the late vs. early group, according to the authors.

Seroconversion and seroprotection occurred less often in the rituximab group than in the methotrexate-treated group for both influenza A strains. Seroprotection occurred less often in the rituximab group than in the healthy controls for the A(H1N1) strains, the authors wrote. Of the three cases of seroconversion and six cases of seroprotection observed in the rituximab group, all but one of the seroprotection cases occurred in the late rituximab subgroup, they stated.

An examination of vaccination safety showed no differences among the three groups regarding the occurrence of side effects, the authors wrote. Also, disease activity in the methotrexate and rituximab groups, assessed with the DAS28 prior to and 7 and 28 days after vaccination, was not influenced by vaccination.

Because patients who were treated with rituximab appear to have a “severely hampered” humoral immune response to the trivalent subunit influenza vaccination, preemptive influenza vaccination should be considered prior to rituximab administration, the authors wrote, noting the importance of yearly influenza vaccination, given the increase in anti-influenza titers observed in previously vaccinated patients.

In the second study, a controlled trial by Dr. Clifton O. Bingham III of Johns Hopkins University, Baltimore, and colleagues, the investigators examined the immunization responses (humoral immunity and the cellular immune response) of rituximab-treated RA patients who received tetanus toxoid, 23-valent pneumococcal polysaccharide (PPV23), and keyhole limpet hemocyanin (KLH) vaccines, and they evaluated the effects of rituximab-induced CD20+ B-cell depletion on immune responses to these vaccinations (Arthritis Rheum. 2010;62:62–74).

The study enrolled 103 patients aged 18–65 years who had active RA and were receiving a stable dosage of 10–25 mg/wk of methotrexate from 26 U.S. centers between January 2006 and December 2007. Patients were stratified by site and age (18–50 years and 51–65 years) and then were randomized in a 2:1 manner to receive either two cycles of 1,000 mg rituximab (open label) 2 weeks apart plus a stable dose of methotrexate (68 patients), or methotrexate alone (32 patients). In the rituximab-plus-methotrexate group, 100 mg of methylprednisolone was administered intravenously before each rituximab infusion, the authors wrote.

Patients in both groups received the tetanus toxoid adsorbed vaccine, PPV23, KLH, and a Candida albicans skin test according to the protocol schedule. Antitetanus, antipneumonococcal, and anti-KLH serum IgG levels were measured prior to and 4 weeks following each respective vaccine administration, and the delayed-type hypersensitivity (DTH) skin test response was measured 2–3 days following placement, the authors wrote.

An analysis of the results showed that patients in both groups responded similarly to tetanus toxoid vaccine, with 25 patients in the rituximab group (39%) and 11 patients in the methotrexate-only group (42%) showing a more than fourfold risk in antitetanus IgG titer, and 35 rituximab patients and 16 methotrexate patients demonstrating a more than twofold rise, the authors reported. Similarly, they wrote, “the ability to maintain a positive DTH response to the C. albicans skin test was comparable in both groups,” confirming that rituximab had no incremental effect on the patients'ability to mount a DTH response.

Significant differences were observed in the responses to PPV23 between the two groups, with only 57% of patients in the rituximab group demonstrating a twofold rise in titer in response to one or more serotypes, compared with 82% of the methotrexate-only patients, the authors reported. Similarly, only 47% of the rituximab patients had detectable anti-KLH IgG, compared with 93% of the methotrexate-only group, they noted.

“Because neoantigen and polysaccharide responses are B-cell dependent, decreased responses to KLH and [PPV23] are consistent with rituximab's mechanism of action,” the authors observed. “Despite peripheral B-cell depletion, however, responses to the KLH and [PPV23] vaccine were not completely abrogated in the present study,” they wrote, referring to the 47% of rituximab patients who had a quantifiable anti-KLH response and the 57% and 43% of rituximab patients who mounted responses to at least one and two pneumococcal serotypes, respectively. The authors concluded that for maximized vaccination response, “polysaccharide and primary immunizations should be administered prior to rituximab infusions.”

Although both of these studies provide some insight into the effects of rituximab therapy on immune function, “they fall short in offering clues about the causal mechanisms,” Dr. E. William St. Claire of Duke University Medical Center in Durham, N.C., wrote in an editorial (Arthritis Rheum. 2010;62:1–5).

Disclosures: The study reported by Dr. van Assen and colleagues was supported by Roche Nederland and Solvay Pharmaceuticals. The authors reported no additional conflicts of interest. The study reported by Dr. Bingham and colleagues was supported by Genentech Inc. The authors reported having financial relationships with Genentech, Roche, and Merck & Co. One of the authors served on Merck's data and safety monitoring board, and three of the authors own stock or stock options in Genentech. Dr. St. Clair disclosed having financial relationships with Biogen Idec Inc.

Elsevier Global Medical News

Elsevier Global Medical News

Elsevier Global Medical News