Rheumatoid Arthritis

SAN ANTONIO – Adalimumab proved safe and effective when used for up to 2 years for the treatment of psoriatic arthritis in a phase III open-label extension study, according to results reported at the annual meeting of the American Academy of Dermatology.

In 395 patients who completed 2 years of treatment with adalimumab (Humira) for the 120-week multinational trial, treatment showed rapid efficacy for psoriatic arthritis (PsA), and the effect was sustained through the duration of the study, said Dr. Philip Mease of the Swedish Medical Center in Seattle.

Among the measures used in the study to assess disease signs and symptoms were the American College of Rheumatology's ACR 20, ACR 50, and ACR 70 response rates, and the Psoriatic Arthritis Response Criteria (PsARC). The percentages of PsARC responders at weeks 48 and 104 were 77% and 81%, respectively, Dr. Mease reported.

Psoriasis disease activity was measured in those with at least a 3% body surface area involvement using the Psoriasis Activity Severity Index (PASI) 50, 75, and 90 and the Physician's Global Assessment of Psoriasis.

The percentage of patients achieving PASI 50, 75, and 90 scores at weeks 48 and 104 were 84%, 69%, and 55%; and 83%, 70%, and 53%, respectively, Dr. Mease said during a poster discussion at the conference. The percentages of patients with a Physician's Global Assessment of clear or almost clear at those time points were 38% and 30%, and 40% and 31%, respectively.

Patients in the study, which was funded by Abbott Laboratories, were participants in either the 24-week Adalimumab Effectiveness in Psoriatic Arthritis Trial or a similar 12-week trial of the drug. Both trials were placebo-controlled trials comparing placebo with 40 mg of adalimumab every other week, and both showed that adalimumab provided statistically and clinically significant improvement, compared with placebo.

Quality of life was also evaluated using a variety of measures. Among them was the Health Assessment Questionnaire, which measures disability. The mean change at both weeks 48 and 104 was −0.4, which surpassed the “minimum clinically important difference level” of −0.3, Dr. Mease noted.

As for safety, a total of 10.6 serious adverse events per 100 patient-years occurred during the course of the study. There were 2.4 serious infectious adverse events per 100 patient-years, 0.5 malignancies other than nonmelanoma skin cancer per 100 patient-years, 0.78 nonmelanoma skin cancers per 100 patient-years, and two deaths–neither of which was thought to be due to adalimumab treatment, Dr. Mease said. “Overall, the take-home message was that safety issues were similar to those in rheumatoid arthritis trials.” The current findings demonstrate that adalimumab is safe, efficacious, and well tolerated for both skin and joint manifestations through 2 years in patients with psoriatic arthritis, Dr. Mease said.

The agent safely controlled skin and joint symptoms in some patients through 2 years of use. DR. MEASE

SAN ANTONIO – Adalimumab proved safe and effective when used for up to 2 years for the treatment of psoriatic arthritis in a phase III open-label extension study, according to results reported at the annual meeting of the American Academy of Dermatology.

In 395 patients who completed 2 years of treatment with adalimumab (Humira) for the 120-week multinational trial, treatment showed rapid efficacy for psoriatic arthritis (PsA), and the effect was sustained through the duration of the study, said Dr. Philip Mease of the Swedish Medical Center in Seattle.

Among the measures used in the study to assess disease signs and symptoms were the American College of Rheumatology's ACR 20, ACR 50, and ACR 70 response rates, and the Psoriatic Arthritis Response Criteria (PsARC). The percentages of PsARC responders at weeks 48 and 104 were 77% and 81%, respectively, Dr. Mease reported.

Psoriasis disease activity was measured in those with at least a 3% body surface area involvement using the Psoriasis Activity Severity Index (PASI) 50, 75, and 90 and the Physician's Global Assessment of Psoriasis.

The percentage of patients achieving PASI 50, 75, and 90 scores at weeks 48 and 104 were 84%, 69%, and 55%; and 83%, 70%, and 53%, respectively, Dr. Mease said during a poster discussion at the conference. The percentages of patients with a Physician's Global Assessment of clear or almost clear at those time points were 38% and 30%, and 40% and 31%, respectively.

Patients in the study, which was funded by Abbott Laboratories, were participants in either the 24-week Adalimumab Effectiveness in Psoriatic Arthritis Trial or a similar 12-week trial of the drug. Both trials were placebo-controlled trials comparing placebo with 40 mg of adalimumab every other week, and both showed that adalimumab provided statistically and clinically significant improvement, compared with placebo.

Quality of life was also evaluated using a variety of measures. Among them was the Health Assessment Questionnaire, which measures disability. The mean change at both weeks 48 and 104 was −0.4, which surpassed the “minimum clinically important difference level” of −0.3, Dr. Mease noted.

As for safety, a total of 10.6 serious adverse events per 100 patient-years occurred during the course of the study. There were 2.4 serious infectious adverse events per 100 patient-years, 0.5 malignancies other than nonmelanoma skin cancer per 100 patient-years, 0.78 nonmelanoma skin cancers per 100 patient-years, and two deaths–neither of which was thought to be due to adalimumab treatment, Dr. Mease said. “Overall, the take-home message was that safety issues were similar to those in rheumatoid arthritis trials.” The current findings demonstrate that adalimumab is safe, efficacious, and well tolerated for both skin and joint manifestations through 2 years in patients with psoriatic arthritis, Dr. Mease said.

The agent safely controlled skin and joint symptoms in some patients through 2 years of use. DR. MEASE

SAN ANTONIO – Adalimumab proved safe and effective when used for up to 2 years for the treatment of psoriatic arthritis in a phase III open-label extension study, according to results reported at the annual meeting of the American Academy of Dermatology.

In 395 patients who completed 2 years of treatment with adalimumab (Humira) for the 120-week multinational trial, treatment showed rapid efficacy for psoriatic arthritis (PsA), and the effect was sustained through the duration of the study, said Dr. Philip Mease of the Swedish Medical Center in Seattle.

Among the measures used in the study to assess disease signs and symptoms were the American College of Rheumatology's ACR 20, ACR 50, and ACR 70 response rates, and the Psoriatic Arthritis Response Criteria (PsARC). The percentages of PsARC responders at weeks 48 and 104 were 77% and 81%, respectively, Dr. Mease reported.

Psoriasis disease activity was measured in those with at least a 3% body surface area involvement using the Psoriasis Activity Severity Index (PASI) 50, 75, and 90 and the Physician's Global Assessment of Psoriasis.

The percentage of patients achieving PASI 50, 75, and 90 scores at weeks 48 and 104 were 84%, 69%, and 55%; and 83%, 70%, and 53%, respectively, Dr. Mease said during a poster discussion at the conference. The percentages of patients with a Physician's Global Assessment of clear or almost clear at those time points were 38% and 30%, and 40% and 31%, respectively.

Patients in the study, which was funded by Abbott Laboratories, were participants in either the 24-week Adalimumab Effectiveness in Psoriatic Arthritis Trial or a similar 12-week trial of the drug. Both trials were placebo-controlled trials comparing placebo with 40 mg of adalimumab every other week, and both showed that adalimumab provided statistically and clinically significant improvement, compared with placebo.

Quality of life was also evaluated using a variety of measures. Among them was the Health Assessment Questionnaire, which measures disability. The mean change at both weeks 48 and 104 was −0.4, which surpassed the “minimum clinically important difference level” of −0.3, Dr. Mease noted.

As for safety, a total of 10.6 serious adverse events per 100 patient-years occurred during the course of the study. There were 2.4 serious infectious adverse events per 100 patient-years, 0.5 malignancies other than nonmelanoma skin cancer per 100 patient-years, 0.78 nonmelanoma skin cancers per 100 patient-years, and two deaths–neither of which was thought to be due to adalimumab treatment, Dr. Mease said. “Overall, the take-home message was that safety issues were similar to those in rheumatoid arthritis trials.” The current findings demonstrate that adalimumab is safe, efficacious, and well tolerated for both skin and joint manifestations through 2 years in patients with psoriatic arthritis, Dr. Mease said.

The agent safely controlled skin and joint symptoms in some patients through 2 years of use. DR. MEASE

WASHINGTON – Congress is taking a tough look at the use of human growth hormone for a wide variety of conditions, including fibromylagia, which is prompting some concern that payers may react by limiting reimbursement for legitimate purposes.

Human growth hormone (HGH) has been touted as an antiaging cure, and increasingly appears to be used by athletes of all ages in the belief that it helps them improve performance and recover from injuries faster. It has been legitimately studied for injury recovery in the elderly, and also is being investigated as a potential therapy for conditions such as fibromyalgia and chronic fatigue syndrome. But this field of inquiry is relatively new.

Insurers are already reluctant to cover scientifically validated uses of HGH, Dr. Richard Hellman, president of the American Association of Clinical Endocrinologists, said in an interview. The drug can cost $10,000-$20,000 a year. The continuing use for purposes that have little-to-no evidence of safety and effectiveness may ultimately endanger patients who genuinely need HGH, said Dr. Hellman, a clinical professor of medicine at the University of Missouri, Kansas City.

Congress is taking a closer look at HGH and other alleged performance-enhancing substances in the wake of the December report issued by former Sen. George Mitchell that exposed a culture of acceptance for off-label and unproven uses of HGH and anabolic steroids in Major League Baseball.

In mid-February, the House Committee on Oversight and Government Reform held a hearing on what it called “myths and facts” about HGH, vitamin B12, and other substances. The hearing was essentially a warm-up for subsequent panel meetings on the use of such substances in baseball and other professional sports that were scheduled for February, but it touched on issues of interest to physicians.

The hearing provided “an opportunity to provide essential and accurate information not just to professional athletes, but to high school kids, senior citizens, baby boomers turning 60, and everyone in between,” according to Rep. Henry Waxman (D-Calif.), chairman of the oversight committee.

All of these uses are illegal. HGH is the only Food and Drug Administration (FDA) approved product that can only be prescribed for the approved indications. In children, the approved indications are to treat: growth hormone deficiency, chronic kidney disease, Turner syndrome, small for gestational age infants who do not catch up to normal range, Prader-Willi syndrome, idiopathic short stature; SHOX gene haploinsufficiency, and Noonan syndrome. In adults, HGH is legal for AIDS-related wasting syndrome, short-bowel syndrome, and growth hormone deficiency.

Distribution of HGH, or possession with intent to distribute, for any off-label use is a felony, punishable with up to 5 years in prison and fines.

“Without question, those attempting to market or distribute HGH claiming it will aid healing, slow or reverse the aging process, assist in weight loss, or cure depression are scamming consumers and breaking the law,” warned Rep. Tom Davis (R-Va.), the oversight committee's ranking Republican member.

And yet, some estimate that illegal HGH sales far outweigh the sanctioned market. Dr. Thomas Perls told the House committee in February that anti-aging sales amount to $2 billion a year. “I personally have found Web sites of 279 antiaging clinics that advertise HGH treatment, and 26 pharmacies that distribute the drug to these clinics or sometimes directly to users,” said Dr. Perls of Boston University. “I have certainly discovered only a fraction of what exists out there,” he added.

In a JAMA article in 2005, Dr. Perls said that legal sales of HGH in 2004 amounted to about $622 million annually, for a little more than 200,000 initial and refill prescriptions, according to data from IMS Health, a market research company (JAMA 2005;294:2086-90).

Dr. Alan Rogol, a professor of clinical pediatrics at the University of Virginia, Charlottesville, also expressed dismay at the House hearing at what appears to be the growing misuse of HGH. Off-label use comes with increased risk of side effects such as acromegaly, and increased insulin resistance or diabetes, said Dr. Rogol. He also said that in many cases, HGH purchasers were getting something other than HGH. The prices being advertised are too low and, “many of these preparations are taken orally and cannot be the protein hormone HGH, for it is not active by this route,” said Dr. Rogol, who testified on behalf of the Endocrine Society.

Another potential danger is that many of the illicit sales are of human tissue-derived pituitary growth hormone, which has been removed from the market because it has the potential to contain the pathogen that causes Creutzfeldt-Jakob disease. And yet, some of this type of hormone is still available in Eastern Europe and through the Internet.

“It is my opinion for an adult there are no legitimate off-label uses,” Dr. Rogol emphasized in an interview.

But both Dr. Rogol and Dr. Hellman acknowledged that there are no central data on how much HGH is being used illicitly, by either nonphysician or physician prescribers. It's in the public interest to keep a registry or to create some other way to keep track of HGH use, Dr. Hellman said. Physicians legitimately using HGH “should have no problem having their work scrutinized,” he said.

Both endocrinologists also said they were open to considering data on new uses of HGH, as long as it came from a validated scientific process.

The Endocrine Society and AACE both have published guidelines on HGH. The Endocrine Society guidelines, published in 2006, only pertained to treating adult growth hormone deficiency (J. Clin. Endocrinol. Metab. 2006;91:1621-34).

AACE last published guidelines in 2003. That report took a broad look at HGH uses and highlighted concerns that off-label prescribing or abuse could lead to reimbursement issues for legitimate patients (Endocr. Pract. 2003;9:64-76).

WASHINGTON – Congress is taking a tough look at the use of human growth hormone for a wide variety of conditions, including fibromylagia, which is prompting some concern that payers may react by limiting reimbursement for legitimate purposes.

Human growth hormone (HGH) has been touted as an antiaging cure, and increasingly appears to be used by athletes of all ages in the belief that it helps them improve performance and recover from injuries faster. It has been legitimately studied for injury recovery in the elderly, and also is being investigated as a potential therapy for conditions such as fibromyalgia and chronic fatigue syndrome. But this field of inquiry is relatively new.

Insurers are already reluctant to cover scientifically validated uses of HGH, Dr. Richard Hellman, president of the American Association of Clinical Endocrinologists, said in an interview. The drug can cost $10,000-$20,000 a year. The continuing use for purposes that have little-to-no evidence of safety and effectiveness may ultimately endanger patients who genuinely need HGH, said Dr. Hellman, a clinical professor of medicine at the University of Missouri, Kansas City.

Congress is taking a closer look at HGH and other alleged performance-enhancing substances in the wake of the December report issued by former Sen. George Mitchell that exposed a culture of acceptance for off-label and unproven uses of HGH and anabolic steroids in Major League Baseball.

In mid-February, the House Committee on Oversight and Government Reform held a hearing on what it called “myths and facts” about HGH, vitamin B12, and other substances. The hearing was essentially a warm-up for subsequent panel meetings on the use of such substances in baseball and other professional sports that were scheduled for February, but it touched on issues of interest to physicians.

The hearing provided “an opportunity to provide essential and accurate information not just to professional athletes, but to high school kids, senior citizens, baby boomers turning 60, and everyone in between,” according to Rep. Henry Waxman (D-Calif.), chairman of the oversight committee.

All of these uses are illegal. HGH is the only Food and Drug Administration (FDA) approved product that can only be prescribed for the approved indications. In children, the approved indications are to treat: growth hormone deficiency, chronic kidney disease, Turner syndrome, small for gestational age infants who do not catch up to normal range, Prader-Willi syndrome, idiopathic short stature; SHOX gene haploinsufficiency, and Noonan syndrome. In adults, HGH is legal for AIDS-related wasting syndrome, short-bowel syndrome, and growth hormone deficiency.

Distribution of HGH, or possession with intent to distribute, for any off-label use is a felony, punishable with up to 5 years in prison and fines.

“Without question, those attempting to market or distribute HGH claiming it will aid healing, slow or reverse the aging process, assist in weight loss, or cure depression are scamming consumers and breaking the law,” warned Rep. Tom Davis (R-Va.), the oversight committee's ranking Republican member.

And yet, some estimate that illegal HGH sales far outweigh the sanctioned market. Dr. Thomas Perls told the House committee in February that anti-aging sales amount to $2 billion a year. “I personally have found Web sites of 279 antiaging clinics that advertise HGH treatment, and 26 pharmacies that distribute the drug to these clinics or sometimes directly to users,” said Dr. Perls of Boston University. “I have certainly discovered only a fraction of what exists out there,” he added.

In a JAMA article in 2005, Dr. Perls said that legal sales of HGH in 2004 amounted to about $622 million annually, for a little more than 200,000 initial and refill prescriptions, according to data from IMS Health, a market research company (JAMA 2005;294:2086-90).

Dr. Alan Rogol, a professor of clinical pediatrics at the University of Virginia, Charlottesville, also expressed dismay at the House hearing at what appears to be the growing misuse of HGH. Off-label use comes with increased risk of side effects such as acromegaly, and increased insulin resistance or diabetes, said Dr. Rogol. He also said that in many cases, HGH purchasers were getting something other than HGH. The prices being advertised are too low and, “many of these preparations are taken orally and cannot be the protein hormone HGH, for it is not active by this route,” said Dr. Rogol, who testified on behalf of the Endocrine Society.

Another potential danger is that many of the illicit sales are of human tissue-derived pituitary growth hormone, which has been removed from the market because it has the potential to contain the pathogen that causes Creutzfeldt-Jakob disease. And yet, some of this type of hormone is still available in Eastern Europe and through the Internet.

“It is my opinion for an adult there are no legitimate off-label uses,” Dr. Rogol emphasized in an interview.

But both Dr. Rogol and Dr. Hellman acknowledged that there are no central data on how much HGH is being used illicitly, by either nonphysician or physician prescribers. It's in the public interest to keep a registry or to create some other way to keep track of HGH use, Dr. Hellman said. Physicians legitimately using HGH “should have no problem having their work scrutinized,” he said.

Both endocrinologists also said they were open to considering data on new uses of HGH, as long as it came from a validated scientific process.

The Endocrine Society and AACE both have published guidelines on HGH. The Endocrine Society guidelines, published in 2006, only pertained to treating adult growth hormone deficiency (J. Clin. Endocrinol. Metab. 2006;91:1621-34).

AACE last published guidelines in 2003. That report took a broad look at HGH uses and highlighted concerns that off-label prescribing or abuse could lead to reimbursement issues for legitimate patients (Endocr. Pract. 2003;9:64-76).

WASHINGTON – Congress is taking a tough look at the use of human growth hormone for a wide variety of conditions, including fibromylagia, which is prompting some concern that payers may react by limiting reimbursement for legitimate purposes.

Human growth hormone (HGH) has been touted as an antiaging cure, and increasingly appears to be used by athletes of all ages in the belief that it helps them improve performance and recover from injuries faster. It has been legitimately studied for injury recovery in the elderly, and also is being investigated as a potential therapy for conditions such as fibromyalgia and chronic fatigue syndrome. But this field of inquiry is relatively new.

Insurers are already reluctant to cover scientifically validated uses of HGH, Dr. Richard Hellman, president of the American Association of Clinical Endocrinologists, said in an interview. The drug can cost $10,000-$20,000 a year. The continuing use for purposes that have little-to-no evidence of safety and effectiveness may ultimately endanger patients who genuinely need HGH, said Dr. Hellman, a clinical professor of medicine at the University of Missouri, Kansas City.

Congress is taking a closer look at HGH and other alleged performance-enhancing substances in the wake of the December report issued by former Sen. George Mitchell that exposed a culture of acceptance for off-label and unproven uses of HGH and anabolic steroids in Major League Baseball.

In mid-February, the House Committee on Oversight and Government Reform held a hearing on what it called “myths and facts” about HGH, vitamin B12, and other substances. The hearing was essentially a warm-up for subsequent panel meetings on the use of such substances in baseball and other professional sports that were scheduled for February, but it touched on issues of interest to physicians.

The hearing provided “an opportunity to provide essential and accurate information not just to professional athletes, but to high school kids, senior citizens, baby boomers turning 60, and everyone in between,” according to Rep. Henry Waxman (D-Calif.), chairman of the oversight committee.

All of these uses are illegal. HGH is the only Food and Drug Administration (FDA) approved product that can only be prescribed for the approved indications. In children, the approved indications are to treat: growth hormone deficiency, chronic kidney disease, Turner syndrome, small for gestational age infants who do not catch up to normal range, Prader-Willi syndrome, idiopathic short stature; SHOX gene haploinsufficiency, and Noonan syndrome. In adults, HGH is legal for AIDS-related wasting syndrome, short-bowel syndrome, and growth hormone deficiency.

Distribution of HGH, or possession with intent to distribute, for any off-label use is a felony, punishable with up to 5 years in prison and fines.

“Without question, those attempting to market or distribute HGH claiming it will aid healing, slow or reverse the aging process, assist in weight loss, or cure depression are scamming consumers and breaking the law,” warned Rep. Tom Davis (R-Va.), the oversight committee's ranking Republican member.

And yet, some estimate that illegal HGH sales far outweigh the sanctioned market. Dr. Thomas Perls told the House committee in February that anti-aging sales amount to $2 billion a year. “I personally have found Web sites of 279 antiaging clinics that advertise HGH treatment, and 26 pharmacies that distribute the drug to these clinics or sometimes directly to users,” said Dr. Perls of Boston University. “I have certainly discovered only a fraction of what exists out there,” he added.

In a JAMA article in 2005, Dr. Perls said that legal sales of HGH in 2004 amounted to about $622 million annually, for a little more than 200,000 initial and refill prescriptions, according to data from IMS Health, a market research company (JAMA 2005;294:2086-90).

Dr. Alan Rogol, a professor of clinical pediatrics at the University of Virginia, Charlottesville, also expressed dismay at the House hearing at what appears to be the growing misuse of HGH. Off-label use comes with increased risk of side effects such as acromegaly, and increased insulin resistance or diabetes, said Dr. Rogol. He also said that in many cases, HGH purchasers were getting something other than HGH. The prices being advertised are too low and, “many of these preparations are taken orally and cannot be the protein hormone HGH, for it is not active by this route,” said Dr. Rogol, who testified on behalf of the Endocrine Society.

Another potential danger is that many of the illicit sales are of human tissue-derived pituitary growth hormone, which has been removed from the market because it has the potential to contain the pathogen that causes Creutzfeldt-Jakob disease. And yet, some of this type of hormone is still available in Eastern Europe and through the Internet.

“It is my opinion for an adult there are no legitimate off-label uses,” Dr. Rogol emphasized in an interview.

But both Dr. Rogol and Dr. Hellman acknowledged that there are no central data on how much HGH is being used illicitly, by either nonphysician or physician prescribers. It's in the public interest to keep a registry or to create some other way to keep track of HGH use, Dr. Hellman said. Physicians legitimately using HGH “should have no problem having their work scrutinized,” he said.

Both endocrinologists also said they were open to considering data on new uses of HGH, as long as it came from a validated scientific process.

The Endocrine Society and AACE both have published guidelines on HGH. The Endocrine Society guidelines, published in 2006, only pertained to treating adult growth hormone deficiency (J. Clin. Endocrinol. Metab. 2006;91:1621-34).

AACE last published guidelines in 2003. That report took a broad look at HGH uses and highlighted concerns that off-label prescribing or abuse could lead to reimbursement issues for legitimate patients (Endocr. Pract. 2003;9:64-76).

SNOWMASS, COLO. – Reserve an anesthetic block to diagnose sacroiliac joint syndrome for those patients having at least three positive pain-provoking tests on physical examination, Dr. Zacharia Isaac urged at a symposium that was sponsored by the American College of Rheumatology.

“You can avoid a lot of needless diagnostic injections of the SI joint if you examine the patient using a cohort of provocative exam maneuvers,” according to Dr. Isaac, medical director of the comprehensive spine care center at Brigham and Women's Hospital, Boston.

Sacroiliac joint syndrome (SIJS) accounts for around 15% of cases of low back pain, making it the third most common cause after discogenic pain and facet syndrome.

“The SI joint syndrome truly is a dysfunction syndrome because there really is no imaging test that's going to show you that the SI joint is the pain generator. A SPECT [single photon emission computed tomography] scan will not show you a hot SI joint. There will not be a lot of arthritis involving this joint. There will not be a bone scan or any other imaging that will confirm the diagnosis for you. You will not find erosions on MRI. This is not sacroiliitis in any way,” the physical and rehabilitation medicine specialist stressed.

SIJS is characterized by low back and buttock pain that can refer to the groin and thigh. Hip findings are unimpressive. If symptoms are present above the level of the L5 transverse process, it's unlikely the SI joint is the cause. The syndrome often arises posttrauma or intra- or postpartum.

Among the pain-provocative maneuvers useful in identifying suitable candidates for the preferred method diagnostic anesthetic block are Patrick's test, in which the heel of one leg is crossed atop the opposite knee and the top knee is pressed down in an attempt to elicit pain in the sacroiliac area. Another is Gaenslen's test: While the supine patient holds one knee and hip flexed into the abdomen, the other leg hangs over the edge of the examining table as the physician presses down on it to hyperextend the hip and produce pain in the SI joint.

Precise reproduction of the pain upon palpation of a particular spot over the sacral sulcus is another useful indicator of SIJS. Other provocative exam maneuvers include standing extension, SI joint compression, and the joint distraction test.

Dr. Isaac emphasized that the diagnostic intra-articular injection of local anesthetic into the SI joint needs to be performed under fluoroscopic guidance. A positive test is one that results in relief of the familiar pain.

SNOWMASS, COLO. – Reserve an anesthetic block to diagnose sacroiliac joint syndrome for those patients having at least three positive pain-provoking tests on physical examination, Dr. Zacharia Isaac urged at a symposium that was sponsored by the American College of Rheumatology.

“You can avoid a lot of needless diagnostic injections of the SI joint if you examine the patient using a cohort of provocative exam maneuvers,” according to Dr. Isaac, medical director of the comprehensive spine care center at Brigham and Women's Hospital, Boston.

Sacroiliac joint syndrome (SIJS) accounts for around 15% of cases of low back pain, making it the third most common cause after discogenic pain and facet syndrome.

“The SI joint syndrome truly is a dysfunction syndrome because there really is no imaging test that's going to show you that the SI joint is the pain generator. A SPECT [single photon emission computed tomography] scan will not show you a hot SI joint. There will not be a lot of arthritis involving this joint. There will not be a bone scan or any other imaging that will confirm the diagnosis for you. You will not find erosions on MRI. This is not sacroiliitis in any way,” the physical and rehabilitation medicine specialist stressed.

SIJS is characterized by low back and buttock pain that can refer to the groin and thigh. Hip findings are unimpressive. If symptoms are present above the level of the L5 transverse process, it's unlikely the SI joint is the cause. The syndrome often arises posttrauma or intra- or postpartum.

Among the pain-provocative maneuvers useful in identifying suitable candidates for the preferred method diagnostic anesthetic block are Patrick's test, in which the heel of one leg is crossed atop the opposite knee and the top knee is pressed down in an attempt to elicit pain in the sacroiliac area. Another is Gaenslen's test: While the supine patient holds one knee and hip flexed into the abdomen, the other leg hangs over the edge of the examining table as the physician presses down on it to hyperextend the hip and produce pain in the SI joint.

Precise reproduction of the pain upon palpation of a particular spot over the sacral sulcus is another useful indicator of SIJS. Other provocative exam maneuvers include standing extension, SI joint compression, and the joint distraction test.

Dr. Isaac emphasized that the diagnostic intra-articular injection of local anesthetic into the SI joint needs to be performed under fluoroscopic guidance. A positive test is one that results in relief of the familiar pain.

SNOWMASS, COLO. – Reserve an anesthetic block to diagnose sacroiliac joint syndrome for those patients having at least three positive pain-provoking tests on physical examination, Dr. Zacharia Isaac urged at a symposium that was sponsored by the American College of Rheumatology.

“You can avoid a lot of needless diagnostic injections of the SI joint if you examine the patient using a cohort of provocative exam maneuvers,” according to Dr. Isaac, medical director of the comprehensive spine care center at Brigham and Women's Hospital, Boston.

Sacroiliac joint syndrome (SIJS) accounts for around 15% of cases of low back pain, making it the third most common cause after discogenic pain and facet syndrome.

“The SI joint syndrome truly is a dysfunction syndrome because there really is no imaging test that's going to show you that the SI joint is the pain generator. A SPECT [single photon emission computed tomography] scan will not show you a hot SI joint. There will not be a lot of arthritis involving this joint. There will not be a bone scan or any other imaging that will confirm the diagnosis for you. You will not find erosions on MRI. This is not sacroiliitis in any way,” the physical and rehabilitation medicine specialist stressed.

SIJS is characterized by low back and buttock pain that can refer to the groin and thigh. Hip findings are unimpressive. If symptoms are present above the level of the L5 transverse process, it's unlikely the SI joint is the cause. The syndrome often arises posttrauma or intra- or postpartum.

Among the pain-provocative maneuvers useful in identifying suitable candidates for the preferred method diagnostic anesthetic block are Patrick's test, in which the heel of one leg is crossed atop the opposite knee and the top knee is pressed down in an attempt to elicit pain in the sacroiliac area. Another is Gaenslen's test: While the supine patient holds one knee and hip flexed into the abdomen, the other leg hangs over the edge of the examining table as the physician presses down on it to hyperextend the hip and produce pain in the SI joint.

Precise reproduction of the pain upon palpation of a particular spot over the sacral sulcus is another useful indicator of SIJS. Other provocative exam maneuvers include standing extension, SI joint compression, and the joint distraction test.

Dr. Isaac emphasized that the diagnostic intra-articular injection of local anesthetic into the SI joint needs to be performed under fluoroscopic guidance. A positive test is one that results in relief of the familiar pain.

BOSTON – The safety and efficacy of abatacept were maintained throughout 5 years of treatment for patients with rheumatoid arthritis, with more than one-third of those who remained in the long-term extension phase of a multicenter trial achieving an ACR 70 response.

The initial double-blind trial enrolled 339 patients with rheumatoid arthritis (RA) who had had an inadequate response to methotrexate, randomizing them to receive 2 mg/kg abatacept, 10 mg/kg abatacept, or placebo for 1 year. They also received background methotrexate in doses of 10-30 mg/week, Dr. Rene R. Westhovens reported in a poster session at the annual meeting of the American College of Rheumatology.

Abatacept was given as a 30-minute infusion on days 1, 15, and 30, and every 30 days thereafter.

By week 52, 63% of patients receiving the higher dose of abatacept had achieved an ACR 20 response, compared with 36% of those receiving placebo. Moreover, 42% and 21% of those receiving 10 mg/kg of the active drug achieved ACR 50 and 70 responses, respectively, compared with 20% and 8% of those receiving placebo (Arthritis Rheum. 2005;52:2263-71).

Of the 235 patients who completed the double-blind phase of the trial, 219 entered the long-term open-label phase, during which all participants received the 10-mg/kg dose of abatacept plus methotrexate. Among these 219 patients, 84, 68, and 67 were from the original 10-mg/kg, 2-mg/kg, and placebo groups, respectively. Their mean age was 56 years, 74% were female, and their mean disease duration was 10 years. At 5 years, 130 (59%) remained on the drug, reported Dr. Westhovens of University Hospital Gasthuisberg Leuven (Belgium).

The improvements in ACR 20, ACR 50, and ACR 70 responses seen in the 10-mg/kg group in the blinded phase of the trial were maintained at year 5, with response rates of 83%, 65%, and 40%.

During the blinded phase, 55% of patients in the 10-mg/kg group had clinically meaningful improvements in physical function, defined as an increase of 0.3 units or more on the modified Health Assessment Questionnaire Disability Index. This was maintained by 53% at year 5.

The types and incidence of serious adverse events were similar in the double-blind and 5-year cumulative study periods, according to Dr. Westhovens. There were 20 serious adverse events per 100 patient-years reported among patients receiving the active treatment during the double-blind phase of the trial, and 19 serious adverse events per 100 patient-years during the open-label phase.

With almost 60% of patients still participating in the study at 5 years, responses remain durable, demonstrating that “abatacept provides long-term clinical benefits to patients with active RA,” Dr. Westhovens wrote.

He disclosed that he received consulting fees from Bristol-Myers Squibb Co., the sponsor of the study.

BOSTON – The safety and efficacy of abatacept were maintained throughout 5 years of treatment for patients with rheumatoid arthritis, with more than one-third of those who remained in the long-term extension phase of a multicenter trial achieving an ACR 70 response.

The initial double-blind trial enrolled 339 patients with rheumatoid arthritis (RA) who had had an inadequate response to methotrexate, randomizing them to receive 2 mg/kg abatacept, 10 mg/kg abatacept, or placebo for 1 year. They also received background methotrexate in doses of 10-30 mg/week, Dr. Rene R. Westhovens reported in a poster session at the annual meeting of the American College of Rheumatology.

Abatacept was given as a 30-minute infusion on days 1, 15, and 30, and every 30 days thereafter.

By week 52, 63% of patients receiving the higher dose of abatacept had achieved an ACR 20 response, compared with 36% of those receiving placebo. Moreover, 42% and 21% of those receiving 10 mg/kg of the active drug achieved ACR 50 and 70 responses, respectively, compared with 20% and 8% of those receiving placebo (Arthritis Rheum. 2005;52:2263-71).

Of the 235 patients who completed the double-blind phase of the trial, 219 entered the long-term open-label phase, during which all participants received the 10-mg/kg dose of abatacept plus methotrexate. Among these 219 patients, 84, 68, and 67 were from the original 10-mg/kg, 2-mg/kg, and placebo groups, respectively. Their mean age was 56 years, 74% were female, and their mean disease duration was 10 years. At 5 years, 130 (59%) remained on the drug, reported Dr. Westhovens of University Hospital Gasthuisberg Leuven (Belgium).

The improvements in ACR 20, ACR 50, and ACR 70 responses seen in the 10-mg/kg group in the blinded phase of the trial were maintained at year 5, with response rates of 83%, 65%, and 40%.

During the blinded phase, 55% of patients in the 10-mg/kg group had clinically meaningful improvements in physical function, defined as an increase of 0.3 units or more on the modified Health Assessment Questionnaire Disability Index. This was maintained by 53% at year 5.

The types and incidence of serious adverse events were similar in the double-blind and 5-year cumulative study periods, according to Dr. Westhovens. There were 20 serious adverse events per 100 patient-years reported among patients receiving the active treatment during the double-blind phase of the trial, and 19 serious adverse events per 100 patient-years during the open-label phase.

With almost 60% of patients still participating in the study at 5 years, responses remain durable, demonstrating that “abatacept provides long-term clinical benefits to patients with active RA,” Dr. Westhovens wrote.

He disclosed that he received consulting fees from Bristol-Myers Squibb Co., the sponsor of the study.

BOSTON – The safety and efficacy of abatacept were maintained throughout 5 years of treatment for patients with rheumatoid arthritis, with more than one-third of those who remained in the long-term extension phase of a multicenter trial achieving an ACR 70 response.

The initial double-blind trial enrolled 339 patients with rheumatoid arthritis (RA) who had had an inadequate response to methotrexate, randomizing them to receive 2 mg/kg abatacept, 10 mg/kg abatacept, or placebo for 1 year. They also received background methotrexate in doses of 10-30 mg/week, Dr. Rene R. Westhovens reported in a poster session at the annual meeting of the American College of Rheumatology.

Abatacept was given as a 30-minute infusion on days 1, 15, and 30, and every 30 days thereafter.

By week 52, 63% of patients receiving the higher dose of abatacept had achieved an ACR 20 response, compared with 36% of those receiving placebo. Moreover, 42% and 21% of those receiving 10 mg/kg of the active drug achieved ACR 50 and 70 responses, respectively, compared with 20% and 8% of those receiving placebo (Arthritis Rheum. 2005;52:2263-71).

Of the 235 patients who completed the double-blind phase of the trial, 219 entered the long-term open-label phase, during which all participants received the 10-mg/kg dose of abatacept plus methotrexate. Among these 219 patients, 84, 68, and 67 were from the original 10-mg/kg, 2-mg/kg, and placebo groups, respectively. Their mean age was 56 years, 74% were female, and their mean disease duration was 10 years. At 5 years, 130 (59%) remained on the drug, reported Dr. Westhovens of University Hospital Gasthuisberg Leuven (Belgium).

The improvements in ACR 20, ACR 50, and ACR 70 responses seen in the 10-mg/kg group in the blinded phase of the trial were maintained at year 5, with response rates of 83%, 65%, and 40%.

During the blinded phase, 55% of patients in the 10-mg/kg group had clinically meaningful improvements in physical function, defined as an increase of 0.3 units or more on the modified Health Assessment Questionnaire Disability Index. This was maintained by 53% at year 5.

The types and incidence of serious adverse events were similar in the double-blind and 5-year cumulative study periods, according to Dr. Westhovens. There were 20 serious adverse events per 100 patient-years reported among patients receiving the active treatment during the double-blind phase of the trial, and 19 serious adverse events per 100 patient-years during the open-label phase.

With almost 60% of patients still participating in the study at 5 years, responses remain durable, demonstrating that “abatacept provides long-term clinical benefits to patients with active RA,” Dr. Westhovens wrote.

He disclosed that he received consulting fees from Bristol-Myers Squibb Co., the sponsor of the study.

SNOWMASS, COLO. – The many biologic agents for rheumatoid arthritis now in mid- to late-stage development are likely to have little impact on clinical practice unless they are priced substantially lower than those now available, Dr. Mark C. Genovese said at a symposium sponsored by the American College of Rheumatology.

These agents will enter an increasingly crowded biologics marketplace. Data from the phase II and III clinical trials reported to date provide no evidence that the investigational tumor necrosis factor-alpha; inhibitors and anti-CD20 agents are substantially more effective, safer, better tolerated, or more convenient than the ones physicians prescribe today. And that leaves only one major aspect open to competition: expense, said Dr. Genovese, cochief of the division of immunology and rheumatology at Stanford (Calif.) University.

The UCB drug certolizumab (Cimzia) is expected to be the next anti-TNF agent to receive marketing approval for RA. Next to come will probably be Centocor's golimumab, a fully human monoclonal antibody.

Lots of data have been presented on these two agents, with lots more to come. The ACR 20, ACR 50, and ACR 70 response rates are very good–but not profoundly better than the rates for the current anti-TNF biologics. The same holds for the safety profiles. Golimumab, however, has a potential edge in convenience: It appears to be effective when given every 4 weeks rather than every 2 weeks. A subcutaneous version is also being developed, the rheumatologist noted.

Two agents–the humanized monoclonal antibody ocrelizumab and the fully human monoclonal antibody of atumumab–both deplete peripheral B-cells. Thus far the efficacy appears fairly similar for all three, Dr. Genovese said.

In terms of biologics with novel mechanisms of action, on the horizon is tocilizumab (Actemra), a humanized monoclonal antibody that works in RA by blocking the interleukin-6 receptor. Two of the five phase III studies have been presented, with two more to come this June at EULAR in Paris. Dr. Genovese was principal investigator of the largest–the Tocilizumab in Combination With Traditional DMARD (TOWARD) study–which involved 1,220 patients with moderate-to-severe RA who had an inadequate response to a variety of conventional DMARD therapies. The subjects were randomized in a double-blind fashion to placebo or IV tocilizumab at 8 mg/kg every 4 weeks.

“Tocilizumab offers an incredibly useful approach to reducing inflammation, reducing structural damage, and improving symptoms and signs. The efficacy is as we've come to expect of biologics. It looks like there's lots of flexibility regarding the use of background conventional DMARDs,” he commented.

Tocilizumab's impact on clinical practice will depend on the outcome of future studies that will look closer at these safety issues and at how well the biologic works in nonresponders to anti-TNF therap, the application for which most physicians will want to use it first, he said.

Baminercept binds to the lymphotoxin alpha1/beta2 and to LIGHT ligands on activated B and T cells and natural killer cells. In this way it inhibits formation of ectopic lymphoid structures involved in the autoimmune inflammatory cascade. In a 47-patient, short-term, double-blind, placebo-controlled phase II trial sponsored by Biogen Idec, baminercept elicited what Dr. Genovese termed “impressive” responses, with persistent benefits seen 8 weeks after the final dose of the subcutaneously administered, once-monthly biologic.

Belimumab (LymphoStat-B) is a monoclonal antibody that binds to BLyS, a B lymphocyte costimulator of normal and autoimmune B cells.

Dr. Genovese is on the speakers bureaus of Abbott Laboratories, Genentech, Bristol-Myers Squibb Co., Wyeth, and Amgen Inc. He has received research grants from most of those companies as well as Centocor Inc., Biogen Idec, Sereno, and Roche.

The new agents' potential impact on clinical practice will depend on their cost. DR. GENOVESE

SNOWMASS, COLO. – The many biologic agents for rheumatoid arthritis now in mid- to late-stage development are likely to have little impact on clinical practice unless they are priced substantially lower than those now available, Dr. Mark C. Genovese said at a symposium sponsored by the American College of Rheumatology.

These agents will enter an increasingly crowded biologics marketplace. Data from the phase II and III clinical trials reported to date provide no evidence that the investigational tumor necrosis factor-alpha; inhibitors and anti-CD20 agents are substantially more effective, safer, better tolerated, or more convenient than the ones physicians prescribe today. And that leaves only one major aspect open to competition: expense, said Dr. Genovese, cochief of the division of immunology and rheumatology at Stanford (Calif.) University.

The UCB drug certolizumab (Cimzia) is expected to be the next anti-TNF agent to receive marketing approval for RA. Next to come will probably be Centocor's golimumab, a fully human monoclonal antibody.

Lots of data have been presented on these two agents, with lots more to come. The ACR 20, ACR 50, and ACR 70 response rates are very good–but not profoundly better than the rates for the current anti-TNF biologics. The same holds for the safety profiles. Golimumab, however, has a potential edge in convenience: It appears to be effective when given every 4 weeks rather than every 2 weeks. A subcutaneous version is also being developed, the rheumatologist noted.

Two agents–the humanized monoclonal antibody ocrelizumab and the fully human monoclonal antibody of atumumab–both deplete peripheral B-cells. Thus far the efficacy appears fairly similar for all three, Dr. Genovese said.

In terms of biologics with novel mechanisms of action, on the horizon is tocilizumab (Actemra), a humanized monoclonal antibody that works in RA by blocking the interleukin-6 receptor. Two of the five phase III studies have been presented, with two more to come this June at EULAR in Paris. Dr. Genovese was principal investigator of the largest–the Tocilizumab in Combination With Traditional DMARD (TOWARD) study–which involved 1,220 patients with moderate-to-severe RA who had an inadequate response to a variety of conventional DMARD therapies. The subjects were randomized in a double-blind fashion to placebo or IV tocilizumab at 8 mg/kg every 4 weeks.

“Tocilizumab offers an incredibly useful approach to reducing inflammation, reducing structural damage, and improving symptoms and signs. The efficacy is as we've come to expect of biologics. It looks like there's lots of flexibility regarding the use of background conventional DMARDs,” he commented.

Tocilizumab's impact on clinical practice will depend on the outcome of future studies that will look closer at these safety issues and at how well the biologic works in nonresponders to anti-TNF therap, the application for which most physicians will want to use it first, he said.

Baminercept binds to the lymphotoxin alpha1/beta2 and to LIGHT ligands on activated B and T cells and natural killer cells. In this way it inhibits formation of ectopic lymphoid structures involved in the autoimmune inflammatory cascade. In a 47-patient, short-term, double-blind, placebo-controlled phase II trial sponsored by Biogen Idec, baminercept elicited what Dr. Genovese termed “impressive” responses, with persistent benefits seen 8 weeks after the final dose of the subcutaneously administered, once-monthly biologic.

Belimumab (LymphoStat-B) is a monoclonal antibody that binds to BLyS, a B lymphocyte costimulator of normal and autoimmune B cells.

Dr. Genovese is on the speakers bureaus of Abbott Laboratories, Genentech, Bristol-Myers Squibb Co., Wyeth, and Amgen Inc. He has received research grants from most of those companies as well as Centocor Inc., Biogen Idec, Sereno, and Roche.

The new agents' potential impact on clinical practice will depend on their cost. DR. GENOVESE

SNOWMASS, COLO. – The many biologic agents for rheumatoid arthritis now in mid- to late-stage development are likely to have little impact on clinical practice unless they are priced substantially lower than those now available, Dr. Mark C. Genovese said at a symposium sponsored by the American College of Rheumatology.

These agents will enter an increasingly crowded biologics marketplace. Data from the phase II and III clinical trials reported to date provide no evidence that the investigational tumor necrosis factor-alpha; inhibitors and anti-CD20 agents are substantially more effective, safer, better tolerated, or more convenient than the ones physicians prescribe today. And that leaves only one major aspect open to competition: expense, said Dr. Genovese, cochief of the division of immunology and rheumatology at Stanford (Calif.) University.

The UCB drug certolizumab (Cimzia) is expected to be the next anti-TNF agent to receive marketing approval for RA. Next to come will probably be Centocor's golimumab, a fully human monoclonal antibody.

Lots of data have been presented on these two agents, with lots more to come. The ACR 20, ACR 50, and ACR 70 response rates are very good–but not profoundly better than the rates for the current anti-TNF biologics. The same holds for the safety profiles. Golimumab, however, has a potential edge in convenience: It appears to be effective when given every 4 weeks rather than every 2 weeks. A subcutaneous version is also being developed, the rheumatologist noted.

Two agents–the humanized monoclonal antibody ocrelizumab and the fully human monoclonal antibody of atumumab–both deplete peripheral B-cells. Thus far the efficacy appears fairly similar for all three, Dr. Genovese said.

In terms of biologics with novel mechanisms of action, on the horizon is tocilizumab (Actemra), a humanized monoclonal antibody that works in RA by blocking the interleukin-6 receptor. Two of the five phase III studies have been presented, with two more to come this June at EULAR in Paris. Dr. Genovese was principal investigator of the largest–the Tocilizumab in Combination With Traditional DMARD (TOWARD) study–which involved 1,220 patients with moderate-to-severe RA who had an inadequate response to a variety of conventional DMARD therapies. The subjects were randomized in a double-blind fashion to placebo or IV tocilizumab at 8 mg/kg every 4 weeks.

“Tocilizumab offers an incredibly useful approach to reducing inflammation, reducing structural damage, and improving symptoms and signs. The efficacy is as we've come to expect of biologics. It looks like there's lots of flexibility regarding the use of background conventional DMARDs,” he commented.

Tocilizumab's impact on clinical practice will depend on the outcome of future studies that will look closer at these safety issues and at how well the biologic works in nonresponders to anti-TNF therap, the application for which most physicians will want to use it first, he said.

Baminercept binds to the lymphotoxin alpha1/beta2 and to LIGHT ligands on activated B and T cells and natural killer cells. In this way it inhibits formation of ectopic lymphoid structures involved in the autoimmune inflammatory cascade. In a 47-patient, short-term, double-blind, placebo-controlled phase II trial sponsored by Biogen Idec, baminercept elicited what Dr. Genovese termed “impressive” responses, with persistent benefits seen 8 weeks after the final dose of the subcutaneously administered, once-monthly biologic.

Belimumab (LymphoStat-B) is a monoclonal antibody that binds to BLyS, a B lymphocyte costimulator of normal and autoimmune B cells.

Dr. Genovese is on the speakers bureaus of Abbott Laboratories, Genentech, Bristol-Myers Squibb Co., Wyeth, and Amgen Inc. He has received research grants from most of those companies as well as Centocor Inc., Biogen Idec, Sereno, and Roche.

The new agents' potential impact on clinical practice will depend on their cost. DR. GENOVESE

Campylobacter and Salmonella infections are the most common contributors to the incidence of reactive arthritis related to foodborne illness, judging from results of a population-based study in two states.

Dr. John M. Townes of Oregon Health and Science University, Portland, and associates conducted telephone interviews with residents of Minnesota and Oregon who had culture-confirmed Campylobacter, Escherichia coli O157, Salmonella, Shigella, and Yersinia infections reported to the Centers for Disease Control and Prevention's Foodborne Disease Active Surveillance Network between 2002 and 2004. Parents or legal guardians provided proxy interviews for those younger than 18 years of age. The researchers invited participants who reported new onset joint pain, joint swelling, back pain, heel pain, and morning stiffness lasting 3 days or more within 8 weeks of culture to complete a detailed questionnaire and physical examination.

Overall, 6,379 culture-confirmed infections were reported to FoodNet in Minnesota and Oregon between 2002 and 2004. The majority were caused by Campylobacter (53%) and Salmonella (30%), followed by E. coli O157 (9%), Shigella (7%), and Yersinia (1%). A total of 4,468 subjects (70%) were interviewed within 2 months of specimen collection. Of these, 575 (13%) reported having new onset of rheumatologic symptoms suggestive of reactive arthritis, which the investigators defined as a history or physical examination findings consistent with monoarthritis, oligoarthritis, dactylitis, enthesitis, or inflammatory back pain without other rheumatologic explanation. The adjusted odds ratio for having these symptoms was higher for subjects aged 18 years and older (OR 2.5), females (OR 1.5), and those who had signs of severe illness including fever, chills, headache, bloody stools, and persistent diarrhea at the time of screening (OR of these symptoms ranged from 1.6 to 2.8). Risk of having new onset of rheumatologic symptoms was not associated with antibiotic use or HLA-B27 (Ann. Rheum. Dis. 2008 Feb. 13 [doi:10.1136/ard.2007.083451

In a subset of 54 patients who met the criteria for the diagnosis of reactive arthritis based on history and physical examinations, Campylobacter was the most common organism of infection (33 cases), followed by Salmonella (17 cases), Shigella (2 cases), E. coli O157 (1 case), and Yersinia (1 case). Most cases were adults (96%) and female (67%). Enthesitis was the most frequent finding on physical exam (48 cases). Arthritis was seen in 10 cases. The incidence of reactive arthritis following culture-confirmed infections of Campylobacter, E. coli O157, Salmonella, Shigella, and Yersinia was estimated to be from 0.6 to 3.1 cases per 100,000 persons.

The researchers acknowledged certain limitations of the study, including the fact that “it is difficult to prove that the rheumatologic symptoms described by our subjects are truly attributable to the antecedent infections,” they reported. “However, by examining a subset of those with subjective symptoms, we were able to provide objective confirmation that the true illness was present, and was not related to alternate rheumatologic diagnoses.”

They also noted the small number of patients in the subset analysis and pointed out there is no universal definition of reactive arthritis. “We elected to include enthesitis and inflammatory back pain in our case definition,” stated the researchers, who had no relevant conflicts. “Including only those with frank arthritis would obviously have resulted in a substantially lower estimate of the incidence.”

The study was supported by the Centers for Disease Control and Prevention and the Oregon Health and Science University General Clinical Research Center.

Campylobacter and Salmonella infections are the most common contributors to the incidence of reactive arthritis related to foodborne illness, judging from results of a population-based study in two states.

Dr. John M. Townes of Oregon Health and Science University, Portland, and associates conducted telephone interviews with residents of Minnesota and Oregon who had culture-confirmed Campylobacter, Escherichia coli O157, Salmonella, Shigella, and Yersinia infections reported to the Centers for Disease Control and Prevention's Foodborne Disease Active Surveillance Network between 2002 and 2004. Parents or legal guardians provided proxy interviews for those younger than 18 years of age. The researchers invited participants who reported new onset joint pain, joint swelling, back pain, heel pain, and morning stiffness lasting 3 days or more within 8 weeks of culture to complete a detailed questionnaire and physical examination.

Overall, 6,379 culture-confirmed infections were reported to FoodNet in Minnesota and Oregon between 2002 and 2004. The majority were caused by Campylobacter (53%) and Salmonella (30%), followed by E. coli O157 (9%), Shigella (7%), and Yersinia (1%). A total of 4,468 subjects (70%) were interviewed within 2 months of specimen collection. Of these, 575 (13%) reported having new onset of rheumatologic symptoms suggestive of reactive arthritis, which the investigators defined as a history or physical examination findings consistent with monoarthritis, oligoarthritis, dactylitis, enthesitis, or inflammatory back pain without other rheumatologic explanation. The adjusted odds ratio for having these symptoms was higher for subjects aged 18 years and older (OR 2.5), females (OR 1.5), and those who had signs of severe illness including fever, chills, headache, bloody stools, and persistent diarrhea at the time of screening (OR of these symptoms ranged from 1.6 to 2.8). Risk of having new onset of rheumatologic symptoms was not associated with antibiotic use or HLA-B27 (Ann. Rheum. Dis. 2008 Feb. 13 [doi:10.1136/ard.2007.083451

In a subset of 54 patients who met the criteria for the diagnosis of reactive arthritis based on history and physical examinations, Campylobacter was the most common organism of infection (33 cases), followed by Salmonella (17 cases), Shigella (2 cases), E. coli O157 (1 case), and Yersinia (1 case). Most cases were adults (96%) and female (67%). Enthesitis was the most frequent finding on physical exam (48 cases). Arthritis was seen in 10 cases. The incidence of reactive arthritis following culture-confirmed infections of Campylobacter, E. coli O157, Salmonella, Shigella, and Yersinia was estimated to be from 0.6 to 3.1 cases per 100,000 persons.

The researchers acknowledged certain limitations of the study, including the fact that “it is difficult to prove that the rheumatologic symptoms described by our subjects are truly attributable to the antecedent infections,” they reported. “However, by examining a subset of those with subjective symptoms, we were able to provide objective confirmation that the true illness was present, and was not related to alternate rheumatologic diagnoses.”

They also noted the small number of patients in the subset analysis and pointed out there is no universal definition of reactive arthritis. “We elected to include enthesitis and inflammatory back pain in our case definition,” stated the researchers, who had no relevant conflicts. “Including only those with frank arthritis would obviously have resulted in a substantially lower estimate of the incidence.”

The study was supported by the Centers for Disease Control and Prevention and the Oregon Health and Science University General Clinical Research Center.

Campylobacter and Salmonella infections are the most common contributors to the incidence of reactive arthritis related to foodborne illness, judging from results of a population-based study in two states.

Dr. John M. Townes of Oregon Health and Science University, Portland, and associates conducted telephone interviews with residents of Minnesota and Oregon who had culture-confirmed Campylobacter, Escherichia coli O157, Salmonella, Shigella, and Yersinia infections reported to the Centers for Disease Control and Prevention's Foodborne Disease Active Surveillance Network between 2002 and 2004. Parents or legal guardians provided proxy interviews for those younger than 18 years of age. The researchers invited participants who reported new onset joint pain, joint swelling, back pain, heel pain, and morning stiffness lasting 3 days or more within 8 weeks of culture to complete a detailed questionnaire and physical examination.

Overall, 6,379 culture-confirmed infections were reported to FoodNet in Minnesota and Oregon between 2002 and 2004. The majority were caused by Campylobacter (53%) and Salmonella (30%), followed by E. coli O157 (9%), Shigella (7%), and Yersinia (1%). A total of 4,468 subjects (70%) were interviewed within 2 months of specimen collection. Of these, 575 (13%) reported having new onset of rheumatologic symptoms suggestive of reactive arthritis, which the investigators defined as a history or physical examination findings consistent with monoarthritis, oligoarthritis, dactylitis, enthesitis, or inflammatory back pain without other rheumatologic explanation. The adjusted odds ratio for having these symptoms was higher for subjects aged 18 years and older (OR 2.5), females (OR 1.5), and those who had signs of severe illness including fever, chills, headache, bloody stools, and persistent diarrhea at the time of screening (OR of these symptoms ranged from 1.6 to 2.8). Risk of having new onset of rheumatologic symptoms was not associated with antibiotic use or HLA-B27 (Ann. Rheum. Dis. 2008 Feb. 13 [doi:10.1136/ard.2007.083451

In a subset of 54 patients who met the criteria for the diagnosis of reactive arthritis based on history and physical examinations, Campylobacter was the most common organism of infection (33 cases), followed by Salmonella (17 cases), Shigella (2 cases), E. coli O157 (1 case), and Yersinia (1 case). Most cases were adults (96%) and female (67%). Enthesitis was the most frequent finding on physical exam (48 cases). Arthritis was seen in 10 cases. The incidence of reactive arthritis following culture-confirmed infections of Campylobacter, E. coli O157, Salmonella, Shigella, and Yersinia was estimated to be from 0.6 to 3.1 cases per 100,000 persons.

The researchers acknowledged certain limitations of the study, including the fact that “it is difficult to prove that the rheumatologic symptoms described by our subjects are truly attributable to the antecedent infections,” they reported. “However, by examining a subset of those with subjective symptoms, we were able to provide objective confirmation that the true illness was present, and was not related to alternate rheumatologic diagnoses.”

They also noted the small number of patients in the subset analysis and pointed out there is no universal definition of reactive arthritis. “We elected to include enthesitis and inflammatory back pain in our case definition,” stated the researchers, who had no relevant conflicts. “Including only those with frank arthritis would obviously have resulted in a substantially lower estimate of the incidence.”

The study was supported by the Centers for Disease Control and Prevention and the Oregon Health and Science University General Clinical Research Center.

Methotrexate's adverse event profile in psoriatic arthritis was different from that in rheumatoid arthritis in a study of more than 1,000 “everyday” patients treated in 30 rheumatology clinics across 13 countries.

“We have suspected for some time that there is differential toxicity, but the studies have not been based in 'everyday practice,' so these data help,” said lead investigator Dr. Philip Helliwell of the University of Leeds (England) in an interview.

In a study that sought to characterize both drug use patterns and side effect profiles in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, Dr. Helliwell and his colleague, Dr. William J. Taylor, of the University of Otago, Wellington (New Zealand), looked at enrollees in the Classification Criteria for Psoriatic Arthritis (CASPAR) study, including 588 consecutive clinic attendees with PsA and 536 controls, who were also clinic attendees with some form of inflammatory arthritis, most often RA.

Details about drug therapy were unavailable for 12% of PsA and 2% of RA patients. However, in the cases where treatment was known, methotrexate (MTX) was the most often prescribed first-line therapy in both diseases, given as the initial therapy to 39% of patients with PsA and 29% of RA patients. The second most often prescribed first-line therapy was sulfasalazine in PsA and corticosteroids in RA (J. Rheum 2008 Jan. 15 [Epub before print]).

Of the 404 patients with psoriatic arthritis who were still taking pharmacotherapy at the study's conclusion, 23% were treated with combination therapy. The most frequent combinations were “MTX/sulfasalazine (33 cases), MTX/steroids (22 cases), and MTX/anti-TNF (16 cases),” wrote the researchers. Triple drug therapy was used in nine PsA patients.

Combination therapy was used in 45% of the 315 RA patients still taking drugs at the study's end, with the most often prescribed regimens being MTX/corticosteroids (74 cases), MTX/antimalarials (33 cases), MTX/sulfasalazine (22 cases), and MTX/anti-TNF (13 cases). Triple drug therapy was used in 26 cases.

Methotrexate monotherapy was used through the study's completion by “a majority … over 50%,” said Dr. Helliwell.

According to Dr. Helliwell, methotrexate's popularity is despite the fact that it is prescribed “off-label” for both PsA and RA in the United Kingdom. “The people who make methotrexate have no incentive to seek regulatory approval because everybody is using it anyway, and [getting approval] is an expensive process,” he said.

In the United States, methotrexate has Food and Drug Administration approval for the treatment of psoriasis and rheumatoid arthritis, including Polyarticular-Course Juvenile Rheumatoid Arthritis, and neoplastic diseases, according to a representative of the Center for Drug Evaluation for Research at the FDA.

As for the second goal of the study—to ascertain the adverse event profile in each drug—the researchers found that while some events were common to both diseases, like renal problems with cyclosporine and gold salts, and skin problems with antimalarials and gold salts, “pulmonary toxicity seen with MTX was confined to the patients with RA,” affecting 4% of RA patients vs. 1% of PsA cases. Also, “although MTX is infrequently discontinued for reasons of inefficacy in both diseases, it was more often discontinued in PsA compared to RA, primarily for reasons of toxicity.”

Hepatic adverse events occurred in 7% of PsA cases vs. 4% of RA cases. “The problem of hepatotoxicity and methotrexate is of particular concern with psoriasis. Dermatologists seem to see much more hepatotoxicity than we as rheumatologists,” said Dr. Helliwell.

“Treatment trials are constrained in ways that may detract from the use of the drug in everyday practice—patients entered into trials are often a very select group with little comorbidity, which confounds extrapolation of drug use to a wide spectrum of patients,” wrote the authors.

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

Methotrexate's adverse event profile in psoriatic arthritis was different from that in rheumatoid arthritis in a study of more than 1,000 “everyday” patients treated in 30 rheumatology clinics across 13 countries.

“We have suspected for some time that there is differential toxicity, but the studies have not been based in 'everyday practice,' so these data help,” said lead investigator Dr. Philip Helliwell of the University of Leeds (England) in an interview.

In a study that sought to characterize both drug use patterns and side effect profiles in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, Dr. Helliwell and his colleague, Dr. William J. Taylor, of the University of Otago, Wellington (New Zealand), looked at enrollees in the Classification Criteria for Psoriatic Arthritis (CASPAR) study, including 588 consecutive clinic attendees with PsA and 536 controls, who were also clinic attendees with some form of inflammatory arthritis, most often RA.

Details about drug therapy were unavailable for 12% of PsA and 2% of RA patients. However, in the cases where treatment was known, methotrexate (MTX) was the most often prescribed first-line therapy in both diseases, given as the initial therapy to 39% of patients with PsA and 29% of RA patients. The second most often prescribed first-line therapy was sulfasalazine in PsA and corticosteroids in RA (J. Rheum 2008 Jan. 15 [Epub before print]).

Of the 404 patients with psoriatic arthritis who were still taking pharmacotherapy at the study's conclusion, 23% were treated with combination therapy. The most frequent combinations were “MTX/sulfasalazine (33 cases), MTX/steroids (22 cases), and MTX/anti-TNF (16 cases),” wrote the researchers. Triple drug therapy was used in nine PsA patients.

Combination therapy was used in 45% of the 315 RA patients still taking drugs at the study's end, with the most often prescribed regimens being MTX/corticosteroids (74 cases), MTX/antimalarials (33 cases), MTX/sulfasalazine (22 cases), and MTX/anti-TNF (13 cases). Triple drug therapy was used in 26 cases.

Methotrexate monotherapy was used through the study's completion by “a majority … over 50%,” said Dr. Helliwell.

According to Dr. Helliwell, methotrexate's popularity is despite the fact that it is prescribed “off-label” for both PsA and RA in the United Kingdom. “The people who make methotrexate have no incentive to seek regulatory approval because everybody is using it anyway, and [getting approval] is an expensive process,” he said.

In the United States, methotrexate has Food and Drug Administration approval for the treatment of psoriasis and rheumatoid arthritis, including Polyarticular-Course Juvenile Rheumatoid Arthritis, and neoplastic diseases, according to a representative of the Center for Drug Evaluation for Research at the FDA.

As for the second goal of the study—to ascertain the adverse event profile in each drug—the researchers found that while some events were common to both diseases, like renal problems with cyclosporine and gold salts, and skin problems with antimalarials and gold salts, “pulmonary toxicity seen with MTX was confined to the patients with RA,” affecting 4% of RA patients vs. 1% of PsA cases. Also, “although MTX is infrequently discontinued for reasons of inefficacy in both diseases, it was more often discontinued in PsA compared to RA, primarily for reasons of toxicity.”

Hepatic adverse events occurred in 7% of PsA cases vs. 4% of RA cases. “The problem of hepatotoxicity and methotrexate is of particular concern with psoriasis. Dermatologists seem to see much more hepatotoxicity than we as rheumatologists,” said Dr. Helliwell.

“Treatment trials are constrained in ways that may detract from the use of the drug in everyday practice—patients entered into trials are often a very select group with little comorbidity, which confounds extrapolation of drug use to a wide spectrum of patients,” wrote the authors.

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

Methotrexate's adverse event profile in psoriatic arthritis was different from that in rheumatoid arthritis in a study of more than 1,000 “everyday” patients treated in 30 rheumatology clinics across 13 countries.

“We have suspected for some time that there is differential toxicity, but the studies have not been based in 'everyday practice,' so these data help,” said lead investigator Dr. Philip Helliwell of the University of Leeds (England) in an interview.

In a study that sought to characterize both drug use patterns and side effect profiles in psoriatic arthritis (PsA) and rheumatoid arthritis (RA) patients, Dr. Helliwell and his colleague, Dr. William J. Taylor, of the University of Otago, Wellington (New Zealand), looked at enrollees in the Classification Criteria for Psoriatic Arthritis (CASPAR) study, including 588 consecutive clinic attendees with PsA and 536 controls, who were also clinic attendees with some form of inflammatory arthritis, most often RA.

Details about drug therapy were unavailable for 12% of PsA and 2% of RA patients. However, in the cases where treatment was known, methotrexate (MTX) was the most often prescribed first-line therapy in both diseases, given as the initial therapy to 39% of patients with PsA and 29% of RA patients. The second most often prescribed first-line therapy was sulfasalazine in PsA and corticosteroids in RA (J. Rheum 2008 Jan. 15 [Epub before print]).

Of the 404 patients with psoriatic arthritis who were still taking pharmacotherapy at the study's conclusion, 23% were treated with combination therapy. The most frequent combinations were “MTX/sulfasalazine (33 cases), MTX/steroids (22 cases), and MTX/anti-TNF (16 cases),” wrote the researchers. Triple drug therapy was used in nine PsA patients.

Combination therapy was used in 45% of the 315 RA patients still taking drugs at the study's end, with the most often prescribed regimens being MTX/corticosteroids (74 cases), MTX/antimalarials (33 cases), MTX/sulfasalazine (22 cases), and MTX/anti-TNF (13 cases). Triple drug therapy was used in 26 cases.

Methotrexate monotherapy was used through the study's completion by “a majority … over 50%,” said Dr. Helliwell.

According to Dr. Helliwell, methotrexate's popularity is despite the fact that it is prescribed “off-label” for both PsA and RA in the United Kingdom. “The people who make methotrexate have no incentive to seek regulatory approval because everybody is using it anyway, and [getting approval] is an expensive process,” he said.

In the United States, methotrexate has Food and Drug Administration approval for the treatment of psoriasis and rheumatoid arthritis, including Polyarticular-Course Juvenile Rheumatoid Arthritis, and neoplastic diseases, according to a representative of the Center for Drug Evaluation for Research at the FDA.

As for the second goal of the study—to ascertain the adverse event profile in each drug—the researchers found that while some events were common to both diseases, like renal problems with cyclosporine and gold salts, and skin problems with antimalarials and gold salts, “pulmonary toxicity seen with MTX was confined to the patients with RA,” affecting 4% of RA patients vs. 1% of PsA cases. Also, “although MTX is infrequently discontinued for reasons of inefficacy in both diseases, it was more often discontinued in PsA compared to RA, primarily for reasons of toxicity.”

Hepatic adverse events occurred in 7% of PsA cases vs. 4% of RA cases. “The problem of hepatotoxicity and methotrexate is of particular concern with psoriasis. Dermatologists seem to see much more hepatotoxicity than we as rheumatologists,” said Dr. Helliwell.

“Treatment trials are constrained in ways that may detract from the use of the drug in everyday practice—patients entered into trials are often a very select group with little comorbidity, which confounds extrapolation of drug use to a wide spectrum of patients,” wrote the authors.

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

“Evidence is insufficient to draw firm conclusions.”

“We did not find any head-to-head randomized controlled trials.”

Those are phrases that commonly appear in a 151-page report, based on a literature review and released by the Agency for Healthcare Research and Quality, titled “Comparative Effectiveness of Drug Therapy for Rheumatoid Arthritis and Psoriatic Arthritis in Adults.”

“The gaps in information for specific [rheumatoid arthritis] therapies are substantial,” wrote the researchers of the RTI International-University of North Carolina Evidence-Based Practice Center, under contract to AHRQ, a part of the U.S. Department of Health and Human Services.

Despite the paucity of data, the researchers draw some conclusions from the best available medical literature about the benefits and harms of three classes of medications for rheumatoid arthritis (RA) and psoriatic arthritis: synthetic formulations of disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids.

For example, they found that combining the synthetic DMARD methotrexate with one of the biologic DMARDs (abatacept, adalimumab, anakinra, etanercept, infliximab, or rituximab) works better to lessen joint damage than does using methotrexate or one of the biologic DMARDs alone.

In addition, they found that methotrexate works as effectively as adalimumab and etanercept for patients with early RA. “Radiographic outcomes, however, were statistically significantly better in patients treated with biologic DMARDs than [in] patients treated with methotrexate,” the researchers wrote.

“How such intermediate outcomes translate to the long-term clinical progression of the disease remains unclear.”

Dr. Steven B. Abramson, director of the division of rheumatology at New York University Medical Center, called the report “very comprehensive and useful” and “reflective of what I think is our common practice. It tries not to tilt toward one therapy or another. It's a good summation of several years of literature.”

Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, Mo., called the report a “good start” and acknowledged the challenge researchers faced in assembling a document “when there is such precious little data comparing therapies directly.

“That's always a limitation of any of these studies, yet clinicians are forced to make these comparisons all the time,” according to Dr. Leonardi.

The team of researchers, led by Dr. Katrina E. Donahue of the department of family medicine at the University of North Carolina at Chapel Hill, reviewed 156 articles in the medical literature based on 103 studies of synthetic DMARDs, biologic DMARDs, and corticosteroids. Of these, 50% were supported by pharmaceutical companies, 20% were supported by government or independent funds, 11% had a combination of pharmaceutical and government funding, and the source of funding could not be determined in the remaining 19% of studies.

Most of the studies were found to be of fair quality, which was defined as susceptible to some bias but probably not sufficient to invalidate their results. Only one-quarter of the studies were rated good quality, which was defined as having the least bias and results that are considered to be valid.

Based on their literature review, the researchers found that combining prednisone with hydroxychloroquine, methotrexate, or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function. They also determined that there are no meaningful clinical differences between methotrexate and either leflunomide or sulfasalazine.

Other findings in the report include the following:

▸ There is not enough evidence to conclude that combining two biologic DMARDs is better than using one biologic DMARD.

▸ An estimated 17 out of every 1,000 people who take a biologic DMARD for 3-12 months develop serious infection. Combining biologic DMARDs increases this risk.

▸ Painful injection-site reactions occur more often among patients who take anakinra (67%), compared with those who take etanercept (22%) or adalimumab (18%).

Dr. Leonardi, who has helped run clinical trials of biologic DMARDs for psoriasis patients, said that while the current data on comparative treatments for RA and psoriatic RA might be limited, dermatologists “have a long way to go” in comparing biologic DMARDs for psoriasis. “We're left to try our own meta-analysis based on safety and efficacy and looking at the types of patients that come into the trials, [asking] how well did things perform? What were the comparable end points at 12, or 14, or 16 weeks? We try to make our own assessments as best as we can without those head-to-head trials. We just don't have that degree of sophistication yet.”

In the report's conclusion, the researchers emphasized the need for long-term studies of arthritis medications, including head-to-head trials “assessing combination therapies involving synthetic DMARDs in comparison with those involving biologic DMARDs,” they wrote. “Adequately powered, long-term [randomized clinical trials] must also examine different treatment strategies with and without corticosteroids, synthetic DMARDs, and biologic DMARDs to determine the best therapy to prevent or minimize debilitating joint damage in patients with RA. Additionally, no head-to-head [randomized clinical trials] have compared one biologic DMARD with another; this is a significant hole in the literature that future research should fill. However, this is less likely to occur because of the expense of biologic DMARDs.”

Dr. Abramson, who is also vice dean for education, faculty and academic affairs at New York University, New York, called the lack of head-to-head trials of biologic DMARDs “a weakness of this field. These are the studies that do need to get done, particularly with respect to x-ray progression.”

To access the full report online, visit www.effectivehealthcare.ahrq.gov/reports/final.cfm

“Evidence is insufficient to draw firm conclusions.”

“We did not find any head-to-head randomized controlled trials.”

Those are phrases that commonly appear in a 151-page report, based on a literature review and released by the Agency for Healthcare Research and Quality, titled “Comparative Effectiveness of Drug Therapy for Rheumatoid Arthritis and Psoriatic Arthritis in Adults.”

“The gaps in information for specific [rheumatoid arthritis] therapies are substantial,” wrote the researchers of the RTI International-University of North Carolina Evidence-Based Practice Center, under contract to AHRQ, a part of the U.S. Department of Health and Human Services.

Despite the paucity of data, the researchers draw some conclusions from the best available medical literature about the benefits and harms of three classes of medications for rheumatoid arthritis (RA) and psoriatic arthritis: synthetic formulations of disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids.

For example, they found that combining the synthetic DMARD methotrexate with one of the biologic DMARDs (abatacept, adalimumab, anakinra, etanercept, infliximab, or rituximab) works better to lessen joint damage than does using methotrexate or one of the biologic DMARDs alone.

In addition, they found that methotrexate works as effectively as adalimumab and etanercept for patients with early RA. “Radiographic outcomes, however, were statistically significantly better in patients treated with biologic DMARDs than [in] patients treated with methotrexate,” the researchers wrote.

“How such intermediate outcomes translate to the long-term clinical progression of the disease remains unclear.”

Dr. Steven B. Abramson, director of the division of rheumatology at New York University Medical Center, called the report “very comprehensive and useful” and “reflective of what I think is our common practice. It tries not to tilt toward one therapy or another. It's a good summation of several years of literature.”

Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, Mo., called the report a “good start” and acknowledged the challenge researchers faced in assembling a document “when there is such precious little data comparing therapies directly.

“That's always a limitation of any of these studies, yet clinicians are forced to make these comparisons all the time,” according to Dr. Leonardi.

The team of researchers, led by Dr. Katrina E. Donahue of the department of family medicine at the University of North Carolina at Chapel Hill, reviewed 156 articles in the medical literature based on 103 studies of synthetic DMARDs, biologic DMARDs, and corticosteroids. Of these, 50% were supported by pharmaceutical companies, 20% were supported by government or independent funds, 11% had a combination of pharmaceutical and government funding, and the source of funding could not be determined in the remaining 19% of studies.

Most of the studies were found to be of fair quality, which was defined as susceptible to some bias but probably not sufficient to invalidate their results. Only one-quarter of the studies were rated good quality, which was defined as having the least bias and results that are considered to be valid.

Based on their literature review, the researchers found that combining prednisone with hydroxychloroquine, methotrexate, or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function. They also determined that there are no meaningful clinical differences between methotrexate and either leflunomide or sulfasalazine.

Other findings in the report include the following:

▸ There is not enough evidence to conclude that combining two biologic DMARDs is better than using one biologic DMARD.

▸ An estimated 17 out of every 1,000 people who take a biologic DMARD for 3-12 months develop serious infection. Combining biologic DMARDs increases this risk.

▸ Painful injection-site reactions occur more often among patients who take anakinra (67%), compared with those who take etanercept (22%) or adalimumab (18%).

Dr. Leonardi, who has helped run clinical trials of biologic DMARDs for psoriasis patients, said that while the current data on comparative treatments for RA and psoriatic RA might be limited, dermatologists “have a long way to go” in comparing biologic DMARDs for psoriasis. “We're left to try our own meta-analysis based on safety and efficacy and looking at the types of patients that come into the trials, [asking] how well did things perform? What were the comparable end points at 12, or 14, or 16 weeks? We try to make our own assessments as best as we can without those head-to-head trials. We just don't have that degree of sophistication yet.”

In the report's conclusion, the researchers emphasized the need for long-term studies of arthritis medications, including head-to-head trials “assessing combination therapies involving synthetic DMARDs in comparison with those involving biologic DMARDs,” they wrote. “Adequately powered, long-term [randomized clinical trials] must also examine different treatment strategies with and without corticosteroids, synthetic DMARDs, and biologic DMARDs to determine the best therapy to prevent or minimize debilitating joint damage in patients with RA. Additionally, no head-to-head [randomized clinical trials] have compared one biologic DMARD with another; this is a significant hole in the literature that future research should fill. However, this is less likely to occur because of the expense of biologic DMARDs.”

Dr. Abramson, who is also vice dean for education, faculty and academic affairs at New York University, New York, called the lack of head-to-head trials of biologic DMARDs “a weakness of this field. These are the studies that do need to get done, particularly with respect to x-ray progression.”

To access the full report online, visit www.effectivehealthcare.ahrq.gov/reports/final.cfm

“Evidence is insufficient to draw firm conclusions.”

“We did not find any head-to-head randomized controlled trials.”

Those are phrases that commonly appear in a 151-page report, based on a literature review and released by the Agency for Healthcare Research and Quality, titled “Comparative Effectiveness of Drug Therapy for Rheumatoid Arthritis and Psoriatic Arthritis in Adults.”

“The gaps in information for specific [rheumatoid arthritis] therapies are substantial,” wrote the researchers of the RTI International-University of North Carolina Evidence-Based Practice Center, under contract to AHRQ, a part of the U.S. Department of Health and Human Services.

Despite the paucity of data, the researchers draw some conclusions from the best available medical literature about the benefits and harms of three classes of medications for rheumatoid arthritis (RA) and psoriatic arthritis: synthetic formulations of disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and corticosteroids.

For example, they found that combining the synthetic DMARD methotrexate with one of the biologic DMARDs (abatacept, adalimumab, anakinra, etanercept, infliximab, or rituximab) works better to lessen joint damage than does using methotrexate or one of the biologic DMARDs alone.

In addition, they found that methotrexate works as effectively as adalimumab and etanercept for patients with early RA. “Radiographic outcomes, however, were statistically significantly better in patients treated with biologic DMARDs than [in] patients treated with methotrexate,” the researchers wrote.

“How such intermediate outcomes translate to the long-term clinical progression of the disease remains unclear.”

Dr. Steven B. Abramson, director of the division of rheumatology at New York University Medical Center, called the report “very comprehensive and useful” and “reflective of what I think is our common practice. It tries not to tilt toward one therapy or another. It's a good summation of several years of literature.”

Dr. Craig Leonardi, a dermatologist in private practice in St. Louis, Mo., called the report a “good start” and acknowledged the challenge researchers faced in assembling a document “when there is such precious little data comparing therapies directly.

“That's always a limitation of any of these studies, yet clinicians are forced to make these comparisons all the time,” according to Dr. Leonardi.

The team of researchers, led by Dr. Katrina E. Donahue of the department of family medicine at the University of North Carolina at Chapel Hill, reviewed 156 articles in the medical literature based on 103 studies of synthetic DMARDs, biologic DMARDs, and corticosteroids. Of these, 50% were supported by pharmaceutical companies, 20% were supported by government or independent funds, 11% had a combination of pharmaceutical and government funding, and the source of funding could not be determined in the remaining 19% of studies.

Most of the studies were found to be of fair quality, which was defined as susceptible to some bias but probably not sufficient to invalidate their results. Only one-quarter of the studies were rated good quality, which was defined as having the least bias and results that are considered to be valid.

Based on their literature review, the researchers found that combining prednisone with hydroxychloroquine, methotrexate, or sulfasalazine works better than using only a synthetic DMARD to reduce joint swelling and tenderness and to improve function. They also determined that there are no meaningful clinical differences between methotrexate and either leflunomide or sulfasalazine.

Other findings in the report include the following:

▸ There is not enough evidence to conclude that combining two biologic DMARDs is better than using one biologic DMARD.

▸ An estimated 17 out of every 1,000 people who take a biologic DMARD for 3-12 months develop serious infection. Combining biologic DMARDs increases this risk.

▸ Painful injection-site reactions occur more often among patients who take anakinra (67%), compared with those who take etanercept (22%) or adalimumab (18%).

Dr. Leonardi, who has helped run clinical trials of biologic DMARDs for psoriasis patients, said that while the current data on comparative treatments for RA and psoriatic RA might be limited, dermatologists “have a long way to go” in comparing biologic DMARDs for psoriasis. “We're left to try our own meta-analysis based on safety and efficacy and looking at the types of patients that come into the trials, [asking] how well did things perform? What were the comparable end points at 12, or 14, or 16 weeks? We try to make our own assessments as best as we can without those head-to-head trials. We just don't have that degree of sophistication yet.”

In the report's conclusion, the researchers emphasized the need for long-term studies of arthritis medications, including head-to-head trials “assessing combination therapies involving synthetic DMARDs in comparison with those involving biologic DMARDs,” they wrote. “Adequately powered, long-term [randomized clinical trials] must also examine different treatment strategies with and without corticosteroids, synthetic DMARDs, and biologic DMARDs to determine the best therapy to prevent or minimize debilitating joint damage in patients with RA. Additionally, no head-to-head [randomized clinical trials] have compared one biologic DMARD with another; this is a significant hole in the literature that future research should fill. However, this is less likely to occur because of the expense of biologic DMARDs.”

Dr. Abramson, who is also vice dean for education, faculty and academic affairs at New York University, New York, called the lack of head-to-head trials of biologic DMARDs “a weakness of this field. These are the studies that do need to get done, particularly with respect to x-ray progression.”

To access the full report online, visit www.effectivehealthcare.ahrq.gov/reports/final.cfm

FORT LAUDERDALE, FLA. — Prediction of which patients with osteoarthritis will progress has been challenging for clinicians. However, there is promise—researchers identified serum and urinary markers independently associated with 5-year radiographic progression of knee osteoarthritis in a study presented at the World Congress on Osteoarthritis.

Combined use of serum type II collagen helical peptide (Helix-II) and urinary crosslinked C-telopeptide (uCTX-II) might predict disease outcome in these patients, Dr. Patrick Garnero said. Helix-II and CTX-II are type II collagen fragments believed to reflect different osteoarthritis breakdown events from the triple helix and the telopeptide regions of knee cartilage.

Dr. Garnero and his associates previously demonstrated that high urinary levels of these markers were associated with highly destructive hip osteoarthritis (Ann. Rheum. Dis. 2006;65:1639-44). However, urinary markers have limitations, including wide variations in urine dilution and some difficulty obtaining precise sampling among elderly patients.

“Based on this, we launched a study to investigate a new serum-based assay,” said Dr. Garnero, a researcher at Synarc Inc. in Lyon, France.

They compared standing anterior-posterior knee x-rays and Helix-II and CTX-II levels among 83 patients with knee osteoarthritis at baseline and at 2, 3, and 5 years. At baseline, mean age was 62 years and 54% were women. In terms of disease severity, the majority (77%) of patients had a baseline Kellgren-Lawrence (KL) score of 3. The remaining patients scored as follows: KL 0, 13%; KL 1, 5%; KL 2, 4%; and KL 4, 1%.

Joint space was measured on radiographs at the narrowest point. Progression was defined as a reduction in tibiofemoral joint space of 2 mm or a need for total knee replacement during follow-up. A total of 24 patients progressed and 59 did not.

“At baseline and 5 years, both markers were higher in patients with progressive disease. It was not significant at baseline, but the average over 5 years was significant,” Dr. Garnero said at the meeting, sponsored by the Osteoarthritis Research Society International.

For example, after adjustment for age, gender, and body mass index, each standard deviation increase in serum Helix-II was associated with a relative risk of 1.69 for progression. Patients with the highest quartile of serum Helix-II levels and a uCTX-II level above the median had a risk of radiologic progression 8 times higher (RR, 7.79).

“The combined measurement of serum helix-II and uCTX-II may be useful to predict disease outcome in knee osteoarthritis,” Dr. Garnero said.

FORT LAUDERDALE, FLA. — Prediction of which patients with osteoarthritis will progress has been challenging for clinicians. However, there is promise—researchers identified serum and urinary markers independently associated with 5-year radiographic progression of knee osteoarthritis in a study presented at the World Congress on Osteoarthritis.

Combined use of serum type II collagen helical peptide (Helix-II) and urinary crosslinked C-telopeptide (uCTX-II) might predict disease outcome in these patients, Dr. Patrick Garnero said. Helix-II and CTX-II are type II collagen fragments believed to reflect different osteoarthritis breakdown events from the triple helix and the telopeptide regions of knee cartilage.

Dr. Garnero and his associates previously demonstrated that high urinary levels of these markers were associated with highly destructive hip osteoarthritis (Ann. Rheum. Dis. 2006;65:1639-44). However, urinary markers have limitations, including wide variations in urine dilution and some difficulty obtaining precise sampling among elderly patients.

“Based on this, we launched a study to investigate a new serum-based assay,” said Dr. Garnero, a researcher at Synarc Inc. in Lyon, France.

They compared standing anterior-posterior knee x-rays and Helix-II and CTX-II levels among 83 patients with knee osteoarthritis at baseline and at 2, 3, and 5 years. At baseline, mean age was 62 years and 54% were women. In terms of disease severity, the majority (77%) of patients had a baseline Kellgren-Lawrence (KL) score of 3. The remaining patients scored as follows: KL 0, 13%; KL 1, 5%; KL 2, 4%; and KL 4, 1%.

Joint space was measured on radiographs at the narrowest point. Progression was defined as a reduction in tibiofemoral joint space of 2 mm or a need for total knee replacement during follow-up. A total of 24 patients progressed and 59 did not.

“At baseline and 5 years, both markers were higher in patients with progressive disease. It was not significant at baseline, but the average over 5 years was significant,” Dr. Garnero said at the meeting, sponsored by the Osteoarthritis Research Society International.

For example, after adjustment for age, gender, and body mass index, each standard deviation increase in serum Helix-II was associated with a relative risk of 1.69 for progression. Patients with the highest quartile of serum Helix-II levels and a uCTX-II level above the median had a risk of radiologic progression 8 times higher (RR, 7.79).

“The combined measurement of serum helix-II and uCTX-II may be useful to predict disease outcome in knee osteoarthritis,” Dr. Garnero said.

FORT LAUDERDALE, FLA. — Prediction of which patients with osteoarthritis will progress has been challenging for clinicians. However, there is promise—researchers identified serum and urinary markers independently associated with 5-year radiographic progression of knee osteoarthritis in a study presented at the World Congress on Osteoarthritis.

Combined use of serum type II collagen helical peptide (Helix-II) and urinary crosslinked C-telopeptide (uCTX-II) might predict disease outcome in these patients, Dr. Patrick Garnero said. Helix-II and CTX-II are type II collagen fragments believed to reflect different osteoarthritis breakdown events from the triple helix and the telopeptide regions of knee cartilage.

Dr. Garnero and his associates previously demonstrated that high urinary levels of these markers were associated with highly destructive hip osteoarthritis (Ann. Rheum. Dis. 2006;65:1639-44). However, urinary markers have limitations, including wide variations in urine dilution and some difficulty obtaining precise sampling among elderly patients.

“Based on this, we launched a study to investigate a new serum-based assay,” said Dr. Garnero, a researcher at Synarc Inc. in Lyon, France.

They compared standing anterior-posterior knee x-rays and Helix-II and CTX-II levels among 83 patients with knee osteoarthritis at baseline and at 2, 3, and 5 years. At baseline, mean age was 62 years and 54% were women. In terms of disease severity, the majority (77%) of patients had a baseline Kellgren-Lawrence (KL) score of 3. The remaining patients scored as follows: KL 0, 13%; KL 1, 5%; KL 2, 4%; and KL 4, 1%.

Joint space was measured on radiographs at the narrowest point. Progression was defined as a reduction in tibiofemoral joint space of 2 mm or a need for total knee replacement during follow-up. A total of 24 patients progressed and 59 did not.

“At baseline and 5 years, both markers were higher in patients with progressive disease. It was not significant at baseline, but the average over 5 years was significant,” Dr. Garnero said at the meeting, sponsored by the Osteoarthritis Research Society International.

For example, after adjustment for age, gender, and body mass index, each standard deviation increase in serum Helix-II was associated with a relative risk of 1.69 for progression. Patients with the highest quartile of serum Helix-II levels and a uCTX-II level above the median had a risk of radiologic progression 8 times higher (RR, 7.79).

“The combined measurement of serum helix-II and uCTX-II may be useful to predict disease outcome in knee osteoarthritis,” Dr. Garnero said.

FORT LAUDERDALE, FLA. — Symmetrical bilateral progression of knee osteoarthritis was a surprising result of a genetic study of hand osteoarthritis patients and their relatives.

“The most surprising [finding] was that progression occurred in a similar manner on both sides. This indicates to me that there is probably a strong genetic factor for progression,” Dr. Virginia Byers Kraus said in an interview during a poster session at the World Congress on Osteoarthritis, Osteoarthritis Research Society International.

Dr. Byers Kraus and associates studied 1,333 hand osteoarthritis patients for a median of 3.8 years. Participants whose osteoarthritis progressed in the medial compartment of one knee were significantly more likely to progress in the medial compartment of the other. The same held true for lateral compartment progressions.

“If you see these individuals [with hand OA], if they have an affected knee, the other is likely to be affected with osteoarthritis and they are likely to progress in parallel,” said Dr. Byers Kraus, an internist in the division of rheumatology, Duke University Medical Center, Durham, N.C. “It's a probable prognostic factor for patients.”

The cohort came from the Genetics of Generalized Osteoarthritis (GOGO) study. A total of 79% were women and the mean age was 69 years. Researchers scored baseline and follow-up radiographs for changes in Kellgren-Lawrence grade, minimal joint space, presence of osteophytes, and joint space narrowing of the medial and lateral knee compartments. They also assessed at least two affected siblings with three-joint bilateral bony enlargements in their hands to assess any genetic correlations.

“We found in a cohort with hand osteoarthritis they were more likely to have osteoarthritis [in other joints] if family members have hand osteoarthritis,” Dr. Byers Kraus said. “When you have a patient with hand osteoarthritis and relatives with hand osteoarthritis, there is an increased likelihood of bilateral knee osteoarthritis.”

The results may also have research implications. In studies of OA patients who don't progress, it's hard to assess the efficacy of a treatment. “This was responsible for the failure of a major trial on Actonel,” said Dr. Byers Kraus. “Age, female gender, obesity—outside of these, we are not good at identifying definite progressors.”

FORT LAUDERDALE, FLA. — Symmetrical bilateral progression of knee osteoarthritis was a surprising result of a genetic study of hand osteoarthritis patients and their relatives.

“The most surprising [finding] was that progression occurred in a similar manner on both sides. This indicates to me that there is probably a strong genetic factor for progression,” Dr. Virginia Byers Kraus said in an interview during a poster session at the World Congress on Osteoarthritis, Osteoarthritis Research Society International.

Dr. Byers Kraus and associates studied 1,333 hand osteoarthritis patients for a median of 3.8 years. Participants whose osteoarthritis progressed in the medial compartment of one knee were significantly more likely to progress in the medial compartment of the other. The same held true for lateral compartment progressions.

“If you see these individuals [with hand OA], if they have an affected knee, the other is likely to be affected with osteoarthritis and they are likely to progress in parallel,” said Dr. Byers Kraus, an internist in the division of rheumatology, Duke University Medical Center, Durham, N.C. “It's a probable prognostic factor for patients.”

The cohort came from the Genetics of Generalized Osteoarthritis (GOGO) study. A total of 79% were women and the mean age was 69 years. Researchers scored baseline and follow-up radiographs for changes in Kellgren-Lawrence grade, minimal joint space, presence of osteophytes, and joint space narrowing of the medial and lateral knee compartments. They also assessed at least two affected siblings with three-joint bilateral bony enlargements in their hands to assess any genetic correlations.

“We found in a cohort with hand osteoarthritis they were more likely to have osteoarthritis [in other joints] if family members have hand osteoarthritis,” Dr. Byers Kraus said. “When you have a patient with hand osteoarthritis and relatives with hand osteoarthritis, there is an increased likelihood of bilateral knee osteoarthritis.”

The results may also have research implications. In studies of OA patients who don't progress, it's hard to assess the efficacy of a treatment. “This was responsible for the failure of a major trial on Actonel,” said Dr. Byers Kraus. “Age, female gender, obesity—outside of these, we are not good at identifying definite progressors.”

FORT LAUDERDALE, FLA. — Symmetrical bilateral progression of knee osteoarthritis was a surprising result of a genetic study of hand osteoarthritis patients and their relatives.

“The most surprising [finding] was that progression occurred in a similar manner on both sides. This indicates to me that there is probably a strong genetic factor for progression,” Dr. Virginia Byers Kraus said in an interview during a poster session at the World Congress on Osteoarthritis, Osteoarthritis Research Society International.

Dr. Byers Kraus and associates studied 1,333 hand osteoarthritis patients for a median of 3.8 years. Participants whose osteoarthritis progressed in the medial compartment of one knee were significantly more likely to progress in the medial compartment of the other. The same held true for lateral compartment progressions.

“If you see these individuals [with hand OA], if they have an affected knee, the other is likely to be affected with osteoarthritis and they are likely to progress in parallel,” said Dr. Byers Kraus, an internist in the division of rheumatology, Duke University Medical Center, Durham, N.C. “It's a probable prognostic factor for patients.”

The cohort came from the Genetics of Generalized Osteoarthritis (GOGO) study. A total of 79% were women and the mean age was 69 years. Researchers scored baseline and follow-up radiographs for changes in Kellgren-Lawrence grade, minimal joint space, presence of osteophytes, and joint space narrowing of the medial and lateral knee compartments. They also assessed at least two affected siblings with three-joint bilateral bony enlargements in their hands to assess any genetic correlations.

“We found in a cohort with hand osteoarthritis they were more likely to have osteoarthritis [in other joints] if family members have hand osteoarthritis,” Dr. Byers Kraus said. “When you have a patient with hand osteoarthritis and relatives with hand osteoarthritis, there is an increased likelihood of bilateral knee osteoarthritis.”

The results may also have research implications. In studies of OA patients who don't progress, it's hard to assess the efficacy of a treatment. “This was responsible for the failure of a major trial on Actonel,” said Dr. Byers Kraus. “Age, female gender, obesity—outside of these, we are not good at identifying definite progressors.”