Rheumatoid Arthritis

Major Finding: RA patients who received methotrexate plus golimumab showed significantly better RAMRIS scores on MRI than did those who received MTX alone, as early as week 12 and continuing through week 24.

Data Source: A substudy of the GO-BEFORE study, involving 318 patients with active RA whose response to treatment was monitored via MRI.

Disclosures: This study was funded by Centocor and Schering-Plough. The investigators reported no other financial disclosures.

Adding golimumab to methotrexate therapy lessened synovitis, osteitis, and bone erosion to a greater degree than did placebo plus methotrexate, a study has shown.

These improvements were evident as early as the 12th week of treatment on serial magnetic resonance imaging exams, which proved to be much more sensitive than conventional radiography at demonstrating the changes, said Dr. Mikkel Ostergaard, professor of rheumatology at Copenhagen University Hospital at Glostrup, Denmark, and his associates.

They reported the results of a substudy of the 1-year GO-BEFORE (Golimumab Before Employing Methotrexate as the First-Line Option in the Treatment of Rheumatoid Arthritis of Early Onset) study, a large randomized controlled trial comparing various combinations of oral methotrexate (MTX), golimumab injections, and placebo in rheumatoid arthritis (RA) patients. GO-BEFORE's findings demonstrated that after 28 weeks, “golimumab in combination with MTX reduced signs and symptoms and radiographic progression of RA in MTX-naive patients, with a safety profile similar to other anti-[tumor necrosis factor] agents,” the investigators said.

Their substudy involved 318 of these subjects who underwent serial MRI evaluations of the wrist and metacarpophalangeal joints at 12 and 24 weeks. Synovitis and osteitis (bone marrow edema), which signal heavy infiltration by inflammatory cells including osteoclasts, are precursors of new bone erosions. These changes are visible on MRI well before conventional radiography can detect them.

The MRIs were assessed by two readers and an adjudicator using the Rheumatoid Arthritis MRI Scoring (RAMRIS) system, “which has demonstrated very good reliability and a high level of sensitivity to change.” Study subjects who received MTX plus golimumab showed significantly better RAMRIS scores than did those who received MTX alone, as early as week 12 and continuing through week 24, Dr. Ostergaard and his colleagues said (Arthritis Rheum. 2011 Aug. 31 [doi 10.1002/art.30592]).

For example, at week 12, synovitis scores decreased by 1.92 points for the wrist and metacarpophalangeal joints and by 0.85 points for the wrist alone with combined therapy, compared with 0.14 points and 0.02 points with MTX alone. Bone edema–osteitis score decreased by 1.82 points with combined therapy but only by 0.56 points with MTX alone, and bone erosion scores decreased by 0.40 points vs. 0.24 points.

“Similar trends were observed in the sensitivity analyses conducted for the mean change in RAMRIS scores from baseline to week 24,” they added.

In a series of MRIs that were representative of the substudy population as a whole, “images show bone edema that was extensive at baseline, markedly decreased at week 12, and nearly resolved at week 24,” they noted.

The researchers emphasized that the substudy confirmed the conclusion of the entire GO-BEFORE clinical trial, but that MRI demonstrated the statistically significant difference between study groups in less than half the time (12 weeks rather than 28 weeks) and using fewer than half the subjects (318 patients rather than 637 patients). This documents that MRI is a more sensitive tool for detecting structural damage than conventional radiography, they said.

Major Finding: RA patients who received methotrexate plus golimumab showed significantly better RAMRIS scores on MRI than did those who received MTX alone, as early as week 12 and continuing through week 24.

Data Source: A substudy of the GO-BEFORE study, involving 318 patients with active RA whose response to treatment was monitored via MRI.

Disclosures: This study was funded by Centocor and Schering-Plough. The investigators reported no other financial disclosures.

Adding golimumab to methotrexate therapy lessened synovitis, osteitis, and bone erosion to a greater degree than did placebo plus methotrexate, a study has shown.

These improvements were evident as early as the 12th week of treatment on serial magnetic resonance imaging exams, which proved to be much more sensitive than conventional radiography at demonstrating the changes, said Dr. Mikkel Ostergaard, professor of rheumatology at Copenhagen University Hospital at Glostrup, Denmark, and his associates.

They reported the results of a substudy of the 1-year GO-BEFORE (Golimumab Before Employing Methotrexate as the First-Line Option in the Treatment of Rheumatoid Arthritis of Early Onset) study, a large randomized controlled trial comparing various combinations of oral methotrexate (MTX), golimumab injections, and placebo in rheumatoid arthritis (RA) patients. GO-BEFORE's findings demonstrated that after 28 weeks, “golimumab in combination with MTX reduced signs and symptoms and radiographic progression of RA in MTX-naive patients, with a safety profile similar to other anti-[tumor necrosis factor] agents,” the investigators said.

Their substudy involved 318 of these subjects who underwent serial MRI evaluations of the wrist and metacarpophalangeal joints at 12 and 24 weeks. Synovitis and osteitis (bone marrow edema), which signal heavy infiltration by inflammatory cells including osteoclasts, are precursors of new bone erosions. These changes are visible on MRI well before conventional radiography can detect them.

The MRIs were assessed by two readers and an adjudicator using the Rheumatoid Arthritis MRI Scoring (RAMRIS) system, “which has demonstrated very good reliability and a high level of sensitivity to change.” Study subjects who received MTX plus golimumab showed significantly better RAMRIS scores than did those who received MTX alone, as early as week 12 and continuing through week 24, Dr. Ostergaard and his colleagues said (Arthritis Rheum. 2011 Aug. 31 [doi 10.1002/art.30592]).

For example, at week 12, synovitis scores decreased by 1.92 points for the wrist and metacarpophalangeal joints and by 0.85 points for the wrist alone with combined therapy, compared with 0.14 points and 0.02 points with MTX alone. Bone edema–osteitis score decreased by 1.82 points with combined therapy but only by 0.56 points with MTX alone, and bone erosion scores decreased by 0.40 points vs. 0.24 points.

“Similar trends were observed in the sensitivity analyses conducted for the mean change in RAMRIS scores from baseline to week 24,” they added.

In a series of MRIs that were representative of the substudy population as a whole, “images show bone edema that was extensive at baseline, markedly decreased at week 12, and nearly resolved at week 24,” they noted.

The researchers emphasized that the substudy confirmed the conclusion of the entire GO-BEFORE clinical trial, but that MRI demonstrated the statistically significant difference between study groups in less than half the time (12 weeks rather than 28 weeks) and using fewer than half the subjects (318 patients rather than 637 patients). This documents that MRI is a more sensitive tool for detecting structural damage than conventional radiography, they said.

Major Finding: RA patients who received methotrexate plus golimumab showed significantly better RAMRIS scores on MRI than did those who received MTX alone, as early as week 12 and continuing through week 24.

Data Source: A substudy of the GO-BEFORE study, involving 318 patients with active RA whose response to treatment was monitored via MRI.

Disclosures: This study was funded by Centocor and Schering-Plough. The investigators reported no other financial disclosures.

Adding golimumab to methotrexate therapy lessened synovitis, osteitis, and bone erosion to a greater degree than did placebo plus methotrexate, a study has shown.

These improvements were evident as early as the 12th week of treatment on serial magnetic resonance imaging exams, which proved to be much more sensitive than conventional radiography at demonstrating the changes, said Dr. Mikkel Ostergaard, professor of rheumatology at Copenhagen University Hospital at Glostrup, Denmark, and his associates.

They reported the results of a substudy of the 1-year GO-BEFORE (Golimumab Before Employing Methotrexate as the First-Line Option in the Treatment of Rheumatoid Arthritis of Early Onset) study, a large randomized controlled trial comparing various combinations of oral methotrexate (MTX), golimumab injections, and placebo in rheumatoid arthritis (RA) patients. GO-BEFORE's findings demonstrated that after 28 weeks, “golimumab in combination with MTX reduced signs and symptoms and radiographic progression of RA in MTX-naive patients, with a safety profile similar to other anti-[tumor necrosis factor] agents,” the investigators said.

Their substudy involved 318 of these subjects who underwent serial MRI evaluations of the wrist and metacarpophalangeal joints at 12 and 24 weeks. Synovitis and osteitis (bone marrow edema), which signal heavy infiltration by inflammatory cells including osteoclasts, are precursors of new bone erosions. These changes are visible on MRI well before conventional radiography can detect them.

The MRIs were assessed by two readers and an adjudicator using the Rheumatoid Arthritis MRI Scoring (RAMRIS) system, “which has demonstrated very good reliability and a high level of sensitivity to change.” Study subjects who received MTX plus golimumab showed significantly better RAMRIS scores than did those who received MTX alone, as early as week 12 and continuing through week 24, Dr. Ostergaard and his colleagues said (Arthritis Rheum. 2011 Aug. 31 [doi 10.1002/art.30592]).

For example, at week 12, synovitis scores decreased by 1.92 points for the wrist and metacarpophalangeal joints and by 0.85 points for the wrist alone with combined therapy, compared with 0.14 points and 0.02 points with MTX alone. Bone edema–osteitis score decreased by 1.82 points with combined therapy but only by 0.56 points with MTX alone, and bone erosion scores decreased by 0.40 points vs. 0.24 points.

“Similar trends were observed in the sensitivity analyses conducted for the mean change in RAMRIS scores from baseline to week 24,” they added.

In a series of MRIs that were representative of the substudy population as a whole, “images show bone edema that was extensive at baseline, markedly decreased at week 12, and nearly resolved at week 24,” they noted.

The researchers emphasized that the substudy confirmed the conclusion of the entire GO-BEFORE clinical trial, but that MRI demonstrated the statistically significant difference between study groups in less than half the time (12 weeks rather than 28 weeks) and using fewer than half the subjects (318 patients rather than 637 patients). This documents that MRI is a more sensitive tool for detecting structural damage than conventional radiography, they said.

Major Finding: Patients had a higher revision risk after a total hip replacement if, at the time of their initial surgery, they had a BMI greater than 30 kg/m

Data Source: Case-control study involving 1,672 patients.

Disclosures: The work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Katz said he has no relevant financial disclosures.

SAN DIEGO – People who are overweight or younger than 75 years when they have a total hip replacement face an increased risk for revision within 12 years; the risk is also increased if cement was used to hold the femoral stem of the implant in place, a study has shown.

Based on the findings, “when you talk to somebody who is in their mid- to late 70s about hip replacement, I think you can say revision is not particularly likely. For a younger person, they should recognize that we may have to go back again. At that point, they'll be older and have greater surgical risk,” said the study's lead author, Dr. Jeffrey Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.

Using hospital records and Medicare claims data, Dr. Katz and his associates examined the presurgery characteristics of 836 people who had initial total hip replacements (THRs) from July 1995 to June 1996 and subsequent revisions sometime before 2009. The researchers then compared those patients to 836 matched controls who also had THRs in the mid-1990s but whose prosthetic hip had not been revised by the time their case had a revision.

Patients who had a prior contralateral hip replacement, who had a prior history of other orthopedic surgery, and who lived with others, instead of alone also had a higher revision risk. Odds ratios were modest but statistically significant, ranging from 1.3 to 1.7.

“Age and weight were not surprising. We thought we might see an effect of sex [since] there is a literature of males being at higher risk, but we did not. There is also literature on comorbidity being associated with revision, which we did not see,” Dr. Katz said at the congress.

The cement finding (OR, 1.4) adds “to what is a rather conflicted literature on the durability of cemented versus uncemented designs,” he said.

Cement techniques – including techniques for reaming out the femur and applying the pressure to the cement – have improved since the mid-1990s, so “you have to be careful interpreting the [cement] data. They may not apply to the way cement is used now,” Dr. Katz said.

The researchers also found a higher risk of revision if, at the time of their initial surgery, patients had a body mass index (BMI) greater than 30 kg/m

Height, weight, and BMI are likely related to the biomechanical load on the implant, Dr. Katz noted. Regarding the greater risk below age 75 years (OR, 1.5), younger, more active patients may be more likely to have a faulty THR fixed. Increased risk for prior contralateral hip replacements (OR, 1.4) or orthopedic surgery (OR, 1.5) may indicate a willingness and ability to undergo surgery.

The added risk from living with others (OR, 1.3) “may represent having the social support in place to deal with rehab and a temporary dependency,” which facilitates elective surgery, he said at the congress, which was sponsored by the Osteoarthritis Research Society International.

The manufacturer of the implants, the initial surgeon's level of experience with the procedure, and the reasons for the revisions were not captured by the study.

Major Finding: Patients had a higher revision risk after a total hip replacement if, at the time of their initial surgery, they had a BMI greater than 30 kg/m

Data Source: Case-control study involving 1,672 patients.

Disclosures: The work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Katz said he has no relevant financial disclosures.

SAN DIEGO – People who are overweight or younger than 75 years when they have a total hip replacement face an increased risk for revision within 12 years; the risk is also increased if cement was used to hold the femoral stem of the implant in place, a study has shown.

Based on the findings, “when you talk to somebody who is in their mid- to late 70s about hip replacement, I think you can say revision is not particularly likely. For a younger person, they should recognize that we may have to go back again. At that point, they'll be older and have greater surgical risk,” said the study's lead author, Dr. Jeffrey Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.

Using hospital records and Medicare claims data, Dr. Katz and his associates examined the presurgery characteristics of 836 people who had initial total hip replacements (THRs) from July 1995 to June 1996 and subsequent revisions sometime before 2009. The researchers then compared those patients to 836 matched controls who also had THRs in the mid-1990s but whose prosthetic hip had not been revised by the time their case had a revision.

Patients who had a prior contralateral hip replacement, who had a prior history of other orthopedic surgery, and who lived with others, instead of alone also had a higher revision risk. Odds ratios were modest but statistically significant, ranging from 1.3 to 1.7.

“Age and weight were not surprising. We thought we might see an effect of sex [since] there is a literature of males being at higher risk, but we did not. There is also literature on comorbidity being associated with revision, which we did not see,” Dr. Katz said at the congress.

The cement finding (OR, 1.4) adds “to what is a rather conflicted literature on the durability of cemented versus uncemented designs,” he said.

Cement techniques – including techniques for reaming out the femur and applying the pressure to the cement – have improved since the mid-1990s, so “you have to be careful interpreting the [cement] data. They may not apply to the way cement is used now,” Dr. Katz said.

The researchers also found a higher risk of revision if, at the time of their initial surgery, patients had a body mass index (BMI) greater than 30 kg/m

Height, weight, and BMI are likely related to the biomechanical load on the implant, Dr. Katz noted. Regarding the greater risk below age 75 years (OR, 1.5), younger, more active patients may be more likely to have a faulty THR fixed. Increased risk for prior contralateral hip replacements (OR, 1.4) or orthopedic surgery (OR, 1.5) may indicate a willingness and ability to undergo surgery.

The added risk from living with others (OR, 1.3) “may represent having the social support in place to deal with rehab and a temporary dependency,” which facilitates elective surgery, he said at the congress, which was sponsored by the Osteoarthritis Research Society International.

The manufacturer of the implants, the initial surgeon's level of experience with the procedure, and the reasons for the revisions were not captured by the study.

Major Finding: Patients had a higher revision risk after a total hip replacement if, at the time of their initial surgery, they had a BMI greater than 30 kg/m

Data Source: Case-control study involving 1,672 patients.

Disclosures: The work was funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Katz said he has no relevant financial disclosures.

SAN DIEGO – People who are overweight or younger than 75 years when they have a total hip replacement face an increased risk for revision within 12 years; the risk is also increased if cement was used to hold the femoral stem of the implant in place, a study has shown.

Based on the findings, “when you talk to somebody who is in their mid- to late 70s about hip replacement, I think you can say revision is not particularly likely. For a younger person, they should recognize that we may have to go back again. At that point, they'll be older and have greater surgical risk,” said the study's lead author, Dr. Jeffrey Katz, professor of medicine and orthopedic surgery at Harvard Medical School, Boston.

Using hospital records and Medicare claims data, Dr. Katz and his associates examined the presurgery characteristics of 836 people who had initial total hip replacements (THRs) from July 1995 to June 1996 and subsequent revisions sometime before 2009. The researchers then compared those patients to 836 matched controls who also had THRs in the mid-1990s but whose prosthetic hip had not been revised by the time their case had a revision.

Patients who had a prior contralateral hip replacement, who had a prior history of other orthopedic surgery, and who lived with others, instead of alone also had a higher revision risk. Odds ratios were modest but statistically significant, ranging from 1.3 to 1.7.

“Age and weight were not surprising. We thought we might see an effect of sex [since] there is a literature of males being at higher risk, but we did not. There is also literature on comorbidity being associated with revision, which we did not see,” Dr. Katz said at the congress.

The cement finding (OR, 1.4) adds “to what is a rather conflicted literature on the durability of cemented versus uncemented designs,” he said.

Cement techniques – including techniques for reaming out the femur and applying the pressure to the cement – have improved since the mid-1990s, so “you have to be careful interpreting the [cement] data. They may not apply to the way cement is used now,” Dr. Katz said.

The researchers also found a higher risk of revision if, at the time of their initial surgery, patients had a body mass index (BMI) greater than 30 kg/m

Height, weight, and BMI are likely related to the biomechanical load on the implant, Dr. Katz noted. Regarding the greater risk below age 75 years (OR, 1.5), younger, more active patients may be more likely to have a faulty THR fixed. Increased risk for prior contralateral hip replacements (OR, 1.4) or orthopedic surgery (OR, 1.5) may indicate a willingness and ability to undergo surgery.

The added risk from living with others (OR, 1.3) “may represent having the social support in place to deal with rehab and a temporary dependency,” which facilitates elective surgery, he said at the congress, which was sponsored by the Osteoarthritis Research Society International.

The manufacturer of the implants, the initial surgeon's level of experience with the procedure, and the reasons for the revisions were not captured by the study.

Major Finding: Serum levels of the inflammatory protein MRP8/14 were elevated in 96% of children with JIA who went on to respond well to methotrexate.

Data Source: Data from a Dutch register of 109 children with JIA.

Disclosures: Dr. Moncrieffe's study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children's Charity.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of 109 previously untreated children with JIA to assess predictors of success with methotrexate. The findings represent a step toward the “ambitious goal” of personalized medicine for JIA, said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Dr. Moncrieffe noted that serum MRP8/14 is “relatively easy to measure,” and that samples do not require cold storage.

High levels of MRP 8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an American College of Rheumatology score of 50 or higher at 6 months on methotrexate, with the likelihood of achieving ACR50 or better increasing with every 500-ng/mL serum increase. Of patients with MRP8/14 levels above 3,000 ng/mL at baseline, 96% went on to achieve an ACR50 or higher response to methotrexate. High serum levels were predictive of response to methotrexate regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam (the Netherlands) presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and her associates enrolled 262 patients who had never been prescribed a biologic agent to control their disease before starting etanercept. The patients had been enrolled in the Dutch Arthritis and Biologicals in Children register, which since 1999 has kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They collected baseline clinical data using the physician's global assessment of disease activity and children's health assessment questionnaire scores. The investigators' goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might predict adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

“It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal,” said Dr. Otten. “However, a still-substantial proportion of patients do not reach the goal of inactive disease.” About a third of the patients in Dr. Otten and colleagues' study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began etanercept treatment before trying disease-modifying antirheumatic drugs improved more than those who had been on them previously. This finding was “really important,” as it indicated “the earlier and more aggressively we treat, the better the patients get,” she said.

Major Finding: Serum levels of the inflammatory protein MRP8/14 were elevated in 96% of children with JIA who went on to respond well to methotrexate.

Data Source: Data from a Dutch register of 109 children with JIA.

Disclosures: Dr. Moncrieffe's study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children's Charity.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of 109 previously untreated children with JIA to assess predictors of success with methotrexate. The findings represent a step toward the “ambitious goal” of personalized medicine for JIA, said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Dr. Moncrieffe noted that serum MRP8/14 is “relatively easy to measure,” and that samples do not require cold storage.

High levels of MRP 8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an American College of Rheumatology score of 50 or higher at 6 months on methotrexate, with the likelihood of achieving ACR50 or better increasing with every 500-ng/mL serum increase. Of patients with MRP8/14 levels above 3,000 ng/mL at baseline, 96% went on to achieve an ACR50 or higher response to methotrexate. High serum levels were predictive of response to methotrexate regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam (the Netherlands) presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and her associates enrolled 262 patients who had never been prescribed a biologic agent to control their disease before starting etanercept. The patients had been enrolled in the Dutch Arthritis and Biologicals in Children register, which since 1999 has kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They collected baseline clinical data using the physician's global assessment of disease activity and children's health assessment questionnaire scores. The investigators' goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might predict adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

“It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal,” said Dr. Otten. “However, a still-substantial proportion of patients do not reach the goal of inactive disease.” About a third of the patients in Dr. Otten and colleagues' study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began etanercept treatment before trying disease-modifying antirheumatic drugs improved more than those who had been on them previously. This finding was “really important,” as it indicated “the earlier and more aggressively we treat, the better the patients get,” she said.

Major Finding: Serum levels of the inflammatory protein MRP8/14 were elevated in 96% of children with JIA who went on to respond well to methotrexate.

Data Source: Data from a Dutch register of 109 children with JIA.

Disclosures: Dr. Moncrieffe's study was sponsored by Sparks-UK, the Big Lottery Fund, Arthritis Research U.K., and the Great Ormond Street Hospital Children's Charity.

BRUGES, BELGIUM – Blood levels of an inflammatory protein have been found to be strongly predictive of how well a child with juvenile idiopathic arthritis will do on methotrexate, U.K. researchers have learned.

Children with higher serum levels of myeloid-related protein 8/14 (MRP8/14) were seen to respond considerably better.

The MRP8/14 findings came from Sparks CHARMS (Childhood Arthritis Response to Medication Study), which used a cohort of 109 previously untreated children with JIA to assess predictors of success with methotrexate. The findings represent a step toward the “ambitious goal” of personalized medicine for JIA, said Halima Moncrieffe, Ph.D., of University College London (Pediatr. Rheum. 2011;9[Suppl. 1]:O10), who presented the data on MRP8/14. Dr. Moncrieffe noted that serum MRP8/14 is “relatively easy to measure,” and that samples do not require cold storage.

High levels of MRP 8/14 were shown to be the most strongly predictive factor in a JIA patient achieving an American College of Rheumatology score of 50 or higher at 6 months on methotrexate, with the likelihood of achieving ACR50 or better increasing with every 500-ng/mL serum increase. Of patients with MRP8/14 levels above 3,000 ng/mL at baseline, 96% went on to achieve an ACR50 or higher response to methotrexate. High serum levels were predictive of response to methotrexate regardless of the type of JIA or age at onset; however, patients with systemic JIA were excluded from the study.

Dr. Marieke Otten of Erasmus University Medical Center in Rotterdam (the Netherlands) presented data on clinical indicators of treatment success or failure with etanercept in a cohort of JIA patients (Pediatr. Rheum. 2011;9[Suppl 1]:O28). Ongoing research is examining the usefulness of baseline MRP levels as response predictors, she noted.

Dr. Otten and her associates enrolled 262 patients who had never been prescribed a biologic agent to control their disease before starting etanercept. The patients had been enrolled in the Dutch Arthritis and Biologicals in Children register, which since 1999 has kept data on all Dutch JIA patients using etanercept. The register is funded in part by an unconditional grant from Abbott.

They collected baseline clinical data using the physician's global assessment of disease activity and children's health assessment questionnaire scores. The investigators' goal was to identify clinical predictors of poor response to etanercept and which clinical characteristics might predict adverse events during treatment. However, the study failed to show any significant associations for adverse effects.

“It has been proven that etanercept is highly effective in juvenile idiopathic arthritis, and under current treatment strategies inactive disease seems to be a realistic treatment goal,” said Dr. Otten. “However, a still-substantial proportion of patients do not reach the goal of inactive disease.” About a third of the patients in Dr. Otten and colleagues' study (32%, n = 85) reached clinically inactive disease after 15 months on etanercept. Another third had an ACR50 response or better but did not reach inactive disease, and the last third (34%, n = 88) reached a poor response, defined as less than ACR50, or stopped etanercept early because of ineffectiveness or adverse effects, she said.

Children who began etanercept treatment before trying disease-modifying antirheumatic drugs improved more than those who had been on them previously. This finding was “really important,” as it indicated “the earlier and more aggressively we treat, the better the patients get,” she said.

Major Finding: TNF

Data Source: A study of 2,224 individuals.

Disclosures: The study was supported by a research grant from the Italian Association for the Defense of Psoriatic Patients, the Interdisciplinary Centre for Clinical Research at the University of Erlangen-Nuremberg (Germany), and the Bath (England) Institute for Rheumatic Diseases. Two researchers were received grants from Wyeth-Pharm GmbH (Germany).

European researchers have confirmed a new independent susceptibility allele for psoriatic arthritis that could possibly represent a new candidate pharmacogenetic marker for the disease.

“In this collaborative work, we replicated the association of TNF*-857T as a susceptibility allele for [psoriatic arthritis (PsA)] independent of the main PSORS1 risk allele,” wrote Emiliano Giardina, Ph.D., of the University of Rome, and his colleagues in an article published online in the journal (doi:10.1002/art.30591).

It's long been known that the strongest and most replicated susceptibility region for psoriatic vulgaris – and by extension PsA – is within the major histocompatibility complex (MHC) region (PSORS1-psoriasis susceptibility region). “This locus maps to chromosome 6p21.3, comprising many different class I antigens associated with disease expression. Human leukocyte antigen (HLA)-C was repetitively reported as the PSORS1 gene and HLA-Cw*06:02 as the susceptibility allele,” they noted.

In this study, the researchers attempted to confirm this finding by assessing allele and genotype frequencies of TNF*-857 in three independent cohorts. They included a German cohort (374 cases and 561 controls), an Italian cohort (400 cases and 400 controls), and a British cohort (135 cases and 354 controls.

The overall cohort of 2,224 individuals of European ancestry was assessed for distribution of HLA-Cw*06:02/PSORS1 risk allele and also was typed for TNF*-857T. The overall allele frequency of TNF*-857T was significantly higher in individuals with PsA (27%) than in control individuals (20%).

The researchers calculated the genotype frequencies of TNF*-857T in samples that were positive and negative for the PSORS1 risk allele, in order to verify the existence of an association independent of the PSORS1 risk allele.

“Overall, the frequency of heterozygous or homozygous carriers of TNF*-857T (TT/CT) in individuals negative for the PSORS1/HLA-C risk allele was significantly higher in PsA patients (30%) than in control subjects (21%),” they reported. This yielded an odds ratio of 1.35

“As expected, the haplotype analysis confirmed TNF*-857T as a susceptibility factor independent of the PSORS1/HLA-C risk allele,” they wrote. Association of PsA to TNF*-857T was significant in individuals not carrying the PSORS1/HLA-C risk allele, with an odds ratio of 1.27.

“Although the functional role of TNF*-857T remains to be determined, previous data could show that the allele T increases the transcription of TNF-alpha.”

In addition, tumor necrosis factor–alpha is known to play a pivotal role in both the activation and extravasation of T cells in the highly vascularized synovium, as well as in subchondral osteoclastogenesis promoting bone erosions. Genes encoding for TNF-alpha, along with other cytokines, could be candidate pharmacogenetic markers.

View on the News

Findings Confrims Earlier Research

A most intriguing aspect of psoriasis epidemiology is that about a quarter of these patients will develop psoriatic arthritis, and this disease clusters in families with remarkably high heritability. Despite evidence for genetic factors in this disease, the search for genes associated with arthritis and not psoriasis has been challenging because almost all PsA patients also have psoriasis. PSORS-1, the MHC region that contains Cw6, the allele with the strongest association with psoriasis, is characterized by long linkage disequilibrium. One report noted an association of PsA with the TNF*-857T allele that was independent of PSORS1. In this multinational study of 909 patients and 1,315 healthy controls, the TNF*-857T allele was found at significantly higher frequency in PsA patients negative for the PSORS1 allele (30%), compared with controls (21%). This study replicates findings in the previous study and is also of note because the TNF*-867T allele increases the transcription of TNF, a pivotal cytokine in the pathogenesis of PsA. Also of possible relevance is that this allele is associated with response to etanercept in RA. The replication of this important association should catalyze additional genetic and pharmacogenetic studies to better understand the diagnostic and functional significance of this allele in psoriatic disease.

CHRISTOPHER T. RITCHLIN, M.D., is professor of medicine, allergy/immunology, and rheumatology at the University of Rochester (N.Y.) He reported having no conflicts of interest that are relevant to this piece.

Vitals

Major Finding: TNF

Data Source: A study of 2,224 individuals.

Disclosures: The study was supported by a research grant from the Italian Association for the Defense of Psoriatic Patients, the Interdisciplinary Centre for Clinical Research at the University of Erlangen-Nuremberg (Germany), and the Bath (England) Institute for Rheumatic Diseases. Two researchers were received grants from Wyeth-Pharm GmbH (Germany).

European researchers have confirmed a new independent susceptibility allele for psoriatic arthritis that could possibly represent a new candidate pharmacogenetic marker for the disease.

“In this collaborative work, we replicated the association of TNF*-857T as a susceptibility allele for [psoriatic arthritis (PsA)] independent of the main PSORS1 risk allele,” wrote Emiliano Giardina, Ph.D., of the University of Rome, and his colleagues in an article published online in the journal (doi:10.1002/art.30591).

It's long been known that the strongest and most replicated susceptibility region for psoriatic vulgaris – and by extension PsA – is within the major histocompatibility complex (MHC) region (PSORS1-psoriasis susceptibility region). “This locus maps to chromosome 6p21.3, comprising many different class I antigens associated with disease expression. Human leukocyte antigen (HLA)-C was repetitively reported as the PSORS1 gene and HLA-Cw*06:02 as the susceptibility allele,” they noted.

In this study, the researchers attempted to confirm this finding by assessing allele and genotype frequencies of TNF*-857 in three independent cohorts. They included a German cohort (374 cases and 561 controls), an Italian cohort (400 cases and 400 controls), and a British cohort (135 cases and 354 controls.

The overall cohort of 2,224 individuals of European ancestry was assessed for distribution of HLA-Cw*06:02/PSORS1 risk allele and also was typed for TNF*-857T. The overall allele frequency of TNF*-857T was significantly higher in individuals with PsA (27%) than in control individuals (20%).

The researchers calculated the genotype frequencies of TNF*-857T in samples that were positive and negative for the PSORS1 risk allele, in order to verify the existence of an association independent of the PSORS1 risk allele.

“Overall, the frequency of heterozygous or homozygous carriers of TNF*-857T (TT/CT) in individuals negative for the PSORS1/HLA-C risk allele was significantly higher in PsA patients (30%) than in control subjects (21%),” they reported. This yielded an odds ratio of 1.35

“As expected, the haplotype analysis confirmed TNF*-857T as a susceptibility factor independent of the PSORS1/HLA-C risk allele,” they wrote. Association of PsA to TNF*-857T was significant in individuals not carrying the PSORS1/HLA-C risk allele, with an odds ratio of 1.27.

“Although the functional role of TNF*-857T remains to be determined, previous data could show that the allele T increases the transcription of TNF-alpha.”

In addition, tumor necrosis factor–alpha is known to play a pivotal role in both the activation and extravasation of T cells in the highly vascularized synovium, as well as in subchondral osteoclastogenesis promoting bone erosions. Genes encoding for TNF-alpha, along with other cytokines, could be candidate pharmacogenetic markers.

View on the News

Findings Confrims Earlier Research

A most intriguing aspect of psoriasis epidemiology is that about a quarter of these patients will develop psoriatic arthritis, and this disease clusters in families with remarkably high heritability. Despite evidence for genetic factors in this disease, the search for genes associated with arthritis and not psoriasis has been challenging because almost all PsA patients also have psoriasis. PSORS-1, the MHC region that contains Cw6, the allele with the strongest association with psoriasis, is characterized by long linkage disequilibrium. One report noted an association of PsA with the TNF*-857T allele that was independent of PSORS1. In this multinational study of 909 patients and 1,315 healthy controls, the TNF*-857T allele was found at significantly higher frequency in PsA patients negative for the PSORS1 allele (30%), compared with controls (21%). This study replicates findings in the previous study and is also of note because the TNF*-867T allele increases the transcription of TNF, a pivotal cytokine in the pathogenesis of PsA. Also of possible relevance is that this allele is associated with response to etanercept in RA. The replication of this important association should catalyze additional genetic and pharmacogenetic studies to better understand the diagnostic and functional significance of this allele in psoriatic disease.

CHRISTOPHER T. RITCHLIN, M.D., is professor of medicine, allergy/immunology, and rheumatology at the University of Rochester (N.Y.) He reported having no conflicts of interest that are relevant to this piece.

Vitals

Major Finding: TNF

Data Source: A study of 2,224 individuals.

Disclosures: The study was supported by a research grant from the Italian Association for the Defense of Psoriatic Patients, the Interdisciplinary Centre for Clinical Research at the University of Erlangen-Nuremberg (Germany), and the Bath (England) Institute for Rheumatic Diseases. Two researchers were received grants from Wyeth-Pharm GmbH (Germany).

European researchers have confirmed a new independent susceptibility allele for psoriatic arthritis that could possibly represent a new candidate pharmacogenetic marker for the disease.

“In this collaborative work, we replicated the association of TNF*-857T as a susceptibility allele for [psoriatic arthritis (PsA)] independent of the main PSORS1 risk allele,” wrote Emiliano Giardina, Ph.D., of the University of Rome, and his colleagues in an article published online in the journal (doi:10.1002/art.30591).

It's long been known that the strongest and most replicated susceptibility region for psoriatic vulgaris – and by extension PsA – is within the major histocompatibility complex (MHC) region (PSORS1-psoriasis susceptibility region). “This locus maps to chromosome 6p21.3, comprising many different class I antigens associated with disease expression. Human leukocyte antigen (HLA)-C was repetitively reported as the PSORS1 gene and HLA-Cw*06:02 as the susceptibility allele,” they noted.

In this study, the researchers attempted to confirm this finding by assessing allele and genotype frequencies of TNF*-857 in three independent cohorts. They included a German cohort (374 cases and 561 controls), an Italian cohort (400 cases and 400 controls), and a British cohort (135 cases and 354 controls.

The overall cohort of 2,224 individuals of European ancestry was assessed for distribution of HLA-Cw*06:02/PSORS1 risk allele and also was typed for TNF*-857T. The overall allele frequency of TNF*-857T was significantly higher in individuals with PsA (27%) than in control individuals (20%).

The researchers calculated the genotype frequencies of TNF*-857T in samples that were positive and negative for the PSORS1 risk allele, in order to verify the existence of an association independent of the PSORS1 risk allele.

“Overall, the frequency of heterozygous or homozygous carriers of TNF*-857T (TT/CT) in individuals negative for the PSORS1/HLA-C risk allele was significantly higher in PsA patients (30%) than in control subjects (21%),” they reported. This yielded an odds ratio of 1.35

“As expected, the haplotype analysis confirmed TNF*-857T as a susceptibility factor independent of the PSORS1/HLA-C risk allele,” they wrote. Association of PsA to TNF*-857T was significant in individuals not carrying the PSORS1/HLA-C risk allele, with an odds ratio of 1.27.

“Although the functional role of TNF*-857T remains to be determined, previous data could show that the allele T increases the transcription of TNF-alpha.”

In addition, tumor necrosis factor–alpha is known to play a pivotal role in both the activation and extravasation of T cells in the highly vascularized synovium, as well as in subchondral osteoclastogenesis promoting bone erosions. Genes encoding for TNF-alpha, along with other cytokines, could be candidate pharmacogenetic markers.

View on the News

Findings Confrims Earlier Research

A most intriguing aspect of psoriasis epidemiology is that about a quarter of these patients will develop psoriatic arthritis, and this disease clusters in families with remarkably high heritability. Despite evidence for genetic factors in this disease, the search for genes associated with arthritis and not psoriasis has been challenging because almost all PsA patients also have psoriasis. PSORS-1, the MHC region that contains Cw6, the allele with the strongest association with psoriasis, is characterized by long linkage disequilibrium. One report noted an association of PsA with the TNF*-857T allele that was independent of PSORS1. In this multinational study of 909 patients and 1,315 healthy controls, the TNF*-857T allele was found at significantly higher frequency in PsA patients negative for the PSORS1 allele (30%), compared with controls (21%). This study replicates findings in the previous study and is also of note because the TNF*-867T allele increases the transcription of TNF, a pivotal cytokine in the pathogenesis of PsA. Also of possible relevance is that this allele is associated with response to etanercept in RA. The replication of this important association should catalyze additional genetic and pharmacogenetic studies to better understand the diagnostic and functional significance of this allele in psoriatic disease.

CHRISTOPHER T. RITCHLIN, M.D., is professor of medicine, allergy/immunology, and rheumatology at the University of Rochester (N.Y.) He reported having no conflicts of interest that are relevant to this piece.

Vitals

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, “support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on,” wrote Dr. Cücile L. Overman of Utrecht (the Netherlands) University, and associates (Ann. Rheum. Dis. 2011 Sept. 14 [doi:10.1136/annrheumdis-2011-200338]).

Dr. Overman of the department of clinical and health psychology at Utrecht University looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire.

The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state-trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hr.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still had depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

“Our data do not support the notion that psychological stress may cause disease flares,” despite “weak” evidence that stress may exacerbate disease activity, they wrote. Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, “we used existing data with relatively long intervals between assessments,” wrote Dr. Overman. “More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes.”

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings “do not generalize to cytokine and hypothalamic-pituitary-adrenal axis functioning,” for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, “support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on,” wrote Dr. Cücile L. Overman of Utrecht (the Netherlands) University, and associates (Ann. Rheum. Dis. 2011 Sept. 14 [doi:10.1136/annrheumdis-2011-200338]).

Dr. Overman of the department of clinical and health psychology at Utrecht University looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire.

The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state-trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hr.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still had depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

“Our data do not support the notion that psychological stress may cause disease flares,” despite “weak” evidence that stress may exacerbate disease activity, they wrote. Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, “we used existing data with relatively long intervals between assessments,” wrote Dr. Overman. “More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes.”

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings “do not generalize to cytokine and hypothalamic-pituitary-adrenal axis functioning,” for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, “support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on,” wrote Dr. Cücile L. Overman of Utrecht (the Netherlands) University, and associates (Ann. Rheum. Dis. 2011 Sept. 14 [doi:10.1136/annrheumdis-2011-200338]).

Dr. Overman of the department of clinical and health psychology at Utrecht University looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire.

The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state-trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hr.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still had depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

“Our data do not support the notion that psychological stress may cause disease flares,” despite “weak” evidence that stress may exacerbate disease activity, they wrote. Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, “we used existing data with relatively long intervals between assessments,” wrote Dr. Overman. “More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes.”

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings “do not generalize to cytokine and hypothalamic-pituitary-adrenal axis functioning,” for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

Unilateral hip arthritis may cause alterations in the joint loading of the contralateral knee before the onset of symptomatic osteoarthritis in that knee, a small study has shown.

This finding could open up the possibility of interventions that could prevent or slow the progression of knee osteoarthritis (OA) in those with unilateral hip arthritis.

The results come from a study of 55 participants, who underwent gait analysis of dynamic joint loading and dual-energy x-ray absorptiometry (DXA) to determine bone mineral density (BMD) of the tibial plateau (Arthritis Rheum. 2011 30 Aug. [doi:10.1002/art.30626]).

“This study demonstrates that in unilateral hip OA, the contralateral knee is subjected to significantly higher dynamic joint loading, as assessed by PAddM [peak external knee adduction moment] and by total medial compartment loads, relative to the ipsilateral knee. Importantly, this asymmetry of knee loading is observed even though the knees are asymptomatic and do not have clinical evidence of OA,” wrote Dr. Najia Shakoor and her coinvestigators at Rush Medical College, Chicago.

Asked to comment on the findings, Dr. Nancy E. Lane noted that “it is not a surprise that changes in gait are present before the disease becomes clinically symptomatic.

“The more we can study gait to provide early detection of OA, we might be able to provide an intervention that might slow the progression of the disease,” noted Dr. Lane, professor of medicine and rheumatology at the University of California, Davis, and director of the center for healthy aging at UC Davis.

While no interventions are approved yet, there are braces and special shoes that may support the knee. In addition, ongoing research is evaluating gait interventions. “They may be efficacious if the interventions are initiated earlier in the disease state,” according to Dr. Lane.

Individuals were included if they had symptomatic OA of the hip, as defined by the American College of Rheumatology's Clinical Criteria for Classification. They also had to have at least 30 mm of pain (on a 100-mm scale) while walking – which corresponds to question 1 of the visual analog format of the hip-directed WOMAC (Western Ontario and McMaster Universities Arthritis) Index. OA was confirmed radiographically.

Exclusion criteria included symptomatic OA of the contralateral hip or either knee with the presence of pain defined as 30 mm (on a 100-mm scale) while walking. They were also excluded if they had radiographic evidence of OA of the contralateral hip or either of the knees, in excess of grade 3, according to the modified Kellgren-Lawrence (KL) scale.

A total of 62 individuals met the study criteria and completed the study. The mean age was 62 years, and more women (60%) were included than men. A total of 55 individuals had both appropriate gait data and evaluation of bone density at bilateral knees.

All individuals had anterior-posterior radiographs of the pelvis, which were evaluated for KL grade at the hips. They also underwent anterior-posterior standing knee radiographs that were evaluated for KL grade at the knees. All participants completed the WOMAC visual analog scale for pain at both knees and both hips. The WOMAC scores were normalized to a 100-mm scale.

Participants also underwent gait analysis to collect three-dimensional kinematics and ground reaction forces using optoelectronic cameras with passive markers and a multicomponent force plate. Passive markers were placed at the lateral-most aspect of the superior iliac crest, the superior aspect of the greater trochanter, the lateral knee joint line, the lateral malleolus, the lateral calcaneus, and the head of the fifth metatarsal.

DXA was used to scan the bilateral proximal tibia and determine BMD. Software was used to determine the subperiostial surface of the tibia. Cortical bone of the subchondral plate was excluded from the measurements, as sclerosis in this region can alter BMD. Therefore, the medial and lateral regions of interest include subchondral trabecular bone.

The primary end point was the PAddM, which is a validated gait parameter that reflects the load at the medial compartment of the knee. This measure has been associated with pain, radiographic severity, and progression of knee OA. The PAddM was defined as the external adduction moment of greatest magnitude during the stance phase of the gait cycle in this study. The coprimary end points were total loading of the medial compartment and medial compartment BMD.

Both primary gait outcomes at the knees – the PAddM and the total medial knee load – were significantly greater for the contralateral knee relative to the ipsilateral knee. Lateral compartment load was also greater for the contralateral knee. In addition, the medial tibial plateau BMD was significantly greater at the contralateral knee relative to the ipsilateral knee, though there were no significant differences at the lateral tibial plateau.

Interestingly, the ratio of the contralateral-to-ipsilateral medial compartment knee BMD was directly correlated with contralateral-to-ipsilateral knee PAddM and contralateral-to-ipsilateral knee medial compartment load, the investigators noted.

In addition, the significant asymmetries observed in the proximal tibial BMD of the contralateral vs. ipsilateral knees provide evidence of substantially altered load history in the knees as well.

“The current study demonstrates that loading asymmetries at the knees begin early in the disease course of hip OA to end-stage disease. These results may have implications for interventional strategies targeted in those with unilateral hip OA in order to prevent or minimize these asymmetries early in the disease course,” the researchers concluded.

The authors and Dr. Lane reported that they have no relevant financial disclosures. The study was sponsored by the National Institutes of Health and the Schweppe Foundation.

Unilateral hip arthritis may cause alterations in the joint loading of the contralateral knee before the onset of symptomatic osteoarthritis in that knee, a small study has shown.

This finding could open up the possibility of interventions that could prevent or slow the progression of knee osteoarthritis (OA) in those with unilateral hip arthritis.

The results come from a study of 55 participants, who underwent gait analysis of dynamic joint loading and dual-energy x-ray absorptiometry (DXA) to determine bone mineral density (BMD) of the tibial plateau (Arthritis Rheum. 2011 30 Aug. [doi:10.1002/art.30626]).

“This study demonstrates that in unilateral hip OA, the contralateral knee is subjected to significantly higher dynamic joint loading, as assessed by PAddM [peak external knee adduction moment] and by total medial compartment loads, relative to the ipsilateral knee. Importantly, this asymmetry of knee loading is observed even though the knees are asymptomatic and do not have clinical evidence of OA,” wrote Dr. Najia Shakoor and her coinvestigators at Rush Medical College, Chicago.

Asked to comment on the findings, Dr. Nancy E. Lane noted that “it is not a surprise that changes in gait are present before the disease becomes clinically symptomatic.

“The more we can study gait to provide early detection of OA, we might be able to provide an intervention that might slow the progression of the disease,” noted Dr. Lane, professor of medicine and rheumatology at the University of California, Davis, and director of the center for healthy aging at UC Davis.

While no interventions are approved yet, there are braces and special shoes that may support the knee. In addition, ongoing research is evaluating gait interventions. “They may be efficacious if the interventions are initiated earlier in the disease state,” according to Dr. Lane.

Individuals were included if they had symptomatic OA of the hip, as defined by the American College of Rheumatology's Clinical Criteria for Classification. They also had to have at least 30 mm of pain (on a 100-mm scale) while walking – which corresponds to question 1 of the visual analog format of the hip-directed WOMAC (Western Ontario and McMaster Universities Arthritis) Index. OA was confirmed radiographically.

Exclusion criteria included symptomatic OA of the contralateral hip or either knee with the presence of pain defined as 30 mm (on a 100-mm scale) while walking. They were also excluded if they had radiographic evidence of OA of the contralateral hip or either of the knees, in excess of grade 3, according to the modified Kellgren-Lawrence (KL) scale.

A total of 62 individuals met the study criteria and completed the study. The mean age was 62 years, and more women (60%) were included than men. A total of 55 individuals had both appropriate gait data and evaluation of bone density at bilateral knees.

All individuals had anterior-posterior radiographs of the pelvis, which were evaluated for KL grade at the hips. They also underwent anterior-posterior standing knee radiographs that were evaluated for KL grade at the knees. All participants completed the WOMAC visual analog scale for pain at both knees and both hips. The WOMAC scores were normalized to a 100-mm scale.

Participants also underwent gait analysis to collect three-dimensional kinematics and ground reaction forces using optoelectronic cameras with passive markers and a multicomponent force plate. Passive markers were placed at the lateral-most aspect of the superior iliac crest, the superior aspect of the greater trochanter, the lateral knee joint line, the lateral malleolus, the lateral calcaneus, and the head of the fifth metatarsal.

DXA was used to scan the bilateral proximal tibia and determine BMD. Software was used to determine the subperiostial surface of the tibia. Cortical bone of the subchondral plate was excluded from the measurements, as sclerosis in this region can alter BMD. Therefore, the medial and lateral regions of interest include subchondral trabecular bone.

The primary end point was the PAddM, which is a validated gait parameter that reflects the load at the medial compartment of the knee. This measure has been associated with pain, radiographic severity, and progression of knee OA. The PAddM was defined as the external adduction moment of greatest magnitude during the stance phase of the gait cycle in this study. The coprimary end points were total loading of the medial compartment and medial compartment BMD.

Both primary gait outcomes at the knees – the PAddM and the total medial knee load – were significantly greater for the contralateral knee relative to the ipsilateral knee. Lateral compartment load was also greater for the contralateral knee. In addition, the medial tibial plateau BMD was significantly greater at the contralateral knee relative to the ipsilateral knee, though there were no significant differences at the lateral tibial plateau.

Interestingly, the ratio of the contralateral-to-ipsilateral medial compartment knee BMD was directly correlated with contralateral-to-ipsilateral knee PAddM and contralateral-to-ipsilateral knee medial compartment load, the investigators noted.

In addition, the significant asymmetries observed in the proximal tibial BMD of the contralateral vs. ipsilateral knees provide evidence of substantially altered load history in the knees as well.

“The current study demonstrates that loading asymmetries at the knees begin early in the disease course of hip OA to end-stage disease. These results may have implications for interventional strategies targeted in those with unilateral hip OA in order to prevent or minimize these asymmetries early in the disease course,” the researchers concluded.

The authors and Dr. Lane reported that they have no relevant financial disclosures. The study was sponsored by the National Institutes of Health and the Schweppe Foundation.

Unilateral hip arthritis may cause alterations in the joint loading of the contralateral knee before the onset of symptomatic osteoarthritis in that knee, a small study has shown.

This finding could open up the possibility of interventions that could prevent or slow the progression of knee osteoarthritis (OA) in those with unilateral hip arthritis.

The results come from a study of 55 participants, who underwent gait analysis of dynamic joint loading and dual-energy x-ray absorptiometry (DXA) to determine bone mineral density (BMD) of the tibial plateau (Arthritis Rheum. 2011 30 Aug. [doi:10.1002/art.30626]).

“This study demonstrates that in unilateral hip OA, the contralateral knee is subjected to significantly higher dynamic joint loading, as assessed by PAddM [peak external knee adduction moment] and by total medial compartment loads, relative to the ipsilateral knee. Importantly, this asymmetry of knee loading is observed even though the knees are asymptomatic and do not have clinical evidence of OA,” wrote Dr. Najia Shakoor and her coinvestigators at Rush Medical College, Chicago.

Asked to comment on the findings, Dr. Nancy E. Lane noted that “it is not a surprise that changes in gait are present before the disease becomes clinically symptomatic.

“The more we can study gait to provide early detection of OA, we might be able to provide an intervention that might slow the progression of the disease,” noted Dr. Lane, professor of medicine and rheumatology at the University of California, Davis, and director of the center for healthy aging at UC Davis.

While no interventions are approved yet, there are braces and special shoes that may support the knee. In addition, ongoing research is evaluating gait interventions. “They may be efficacious if the interventions are initiated earlier in the disease state,” according to Dr. Lane.

Individuals were included if they had symptomatic OA of the hip, as defined by the American College of Rheumatology's Clinical Criteria for Classification. They also had to have at least 30 mm of pain (on a 100-mm scale) while walking – which corresponds to question 1 of the visual analog format of the hip-directed WOMAC (Western Ontario and McMaster Universities Arthritis) Index. OA was confirmed radiographically.

Exclusion criteria included symptomatic OA of the contralateral hip or either knee with the presence of pain defined as 30 mm (on a 100-mm scale) while walking. They were also excluded if they had radiographic evidence of OA of the contralateral hip or either of the knees, in excess of grade 3, according to the modified Kellgren-Lawrence (KL) scale.

A total of 62 individuals met the study criteria and completed the study. The mean age was 62 years, and more women (60%) were included than men. A total of 55 individuals had both appropriate gait data and evaluation of bone density at bilateral knees.

All individuals had anterior-posterior radiographs of the pelvis, which were evaluated for KL grade at the hips. They also underwent anterior-posterior standing knee radiographs that were evaluated for KL grade at the knees. All participants completed the WOMAC visual analog scale for pain at both knees and both hips. The WOMAC scores were normalized to a 100-mm scale.

Participants also underwent gait analysis to collect three-dimensional kinematics and ground reaction forces using optoelectronic cameras with passive markers and a multicomponent force plate. Passive markers were placed at the lateral-most aspect of the superior iliac crest, the superior aspect of the greater trochanter, the lateral knee joint line, the lateral malleolus, the lateral calcaneus, and the head of the fifth metatarsal.

DXA was used to scan the bilateral proximal tibia and determine BMD. Software was used to determine the subperiostial surface of the tibia. Cortical bone of the subchondral plate was excluded from the measurements, as sclerosis in this region can alter BMD. Therefore, the medial and lateral regions of interest include subchondral trabecular bone.

The primary end point was the PAddM, which is a validated gait parameter that reflects the load at the medial compartment of the knee. This measure has been associated with pain, radiographic severity, and progression of knee OA. The PAddM was defined as the external adduction moment of greatest magnitude during the stance phase of the gait cycle in this study. The coprimary end points were total loading of the medial compartment and medial compartment BMD.

Both primary gait outcomes at the knees – the PAddM and the total medial knee load – were significantly greater for the contralateral knee relative to the ipsilateral knee. Lateral compartment load was also greater for the contralateral knee. In addition, the medial tibial plateau BMD was significantly greater at the contralateral knee relative to the ipsilateral knee, though there were no significant differences at the lateral tibial plateau.

Interestingly, the ratio of the contralateral-to-ipsilateral medial compartment knee BMD was directly correlated with contralateral-to-ipsilateral knee PAddM and contralateral-to-ipsilateral knee medial compartment load, the investigators noted.

In addition, the significant asymmetries observed in the proximal tibial BMD of the contralateral vs. ipsilateral knees provide evidence of substantially altered load history in the knees as well.

“The current study demonstrates that loading asymmetries at the knees begin early in the disease course of hip OA to end-stage disease. These results may have implications for interventional strategies targeted in those with unilateral hip OA in order to prevent or minimize these asymmetries early in the disease course,” the researchers concluded.

The authors and Dr. Lane reported that they have no relevant financial disclosures. The study was sponsored by the National Institutes of Health and the Schweppe Foundation.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, "support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on," wrote Dr. Cécile L. Overman, of Utrecht University (the Netherlands), and associates. The report was published online in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 Sept. 14 [doi: 10.1136/annrheumdis-2011-200338]).

Dr. Overman, of the department of clinical and health psychology at Utrecht University, looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire. The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state–trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hour.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still experienced depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

"Our data do not support the notion that psychological stress may cause disease flares," despite "weak" evidence that stress may exacerbate disease activity, they wrote.

Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, "we used existing data with relatively long intervals between assessments," wrote Dr. Overman. "More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes."

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings "do not generalize to cytokine and hypothalamic–pituitary–adrenal axis functioning," for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, "support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on," wrote Dr. Cécile L. Overman, of Utrecht University (the Netherlands), and associates. The report was published online in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 Sept. 14 [doi: 10.1136/annrheumdis-2011-200338]).

Dr. Overman, of the department of clinical and health psychology at Utrecht University, looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire. The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state–trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hour.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still experienced depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

"Our data do not support the notion that psychological stress may cause disease flares," despite "weak" evidence that stress may exacerbate disease activity, they wrote.

Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, "we used existing data with relatively long intervals between assessments," wrote Dr. Overman. "More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes."

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings "do not generalize to cytokine and hypothalamic–pituitary–adrenal axis functioning," for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

In patients with rheumatoid arthritis, higher disease activity scores were associated with more severe depression, both when measured at the same time and when measured 6 months apart, suggesting that the impact the two factors have on each other persists over time.

Similarly, depression predicted increased disease activity later.

The findings, while not necessarily causal, "support the notion that in patients with more severe depressed mood, disease activity is probably greater, not only at the same time but also several months later, and that in patients with more swollen and painful joints, psychological distress is probably greater at the same time and later on," wrote Dr. Cécile L. Overman, of Utrecht University (the Netherlands), and associates. The report was published online in Annals of the Rheumatic Diseases (Ann. Rheum. Dis. 2011 Sept. 14 [doi: 10.1136/annrheumdis-2011-200338]).

Dr. Overman, of the department of clinical and health psychology at Utrecht University, looked at 545 patients with a recent diagnosis of rheumatoid arthritis (RA) recruited between 1990 and 2002 in the Utrecht region. The patients were enrolled in a prospective drug trial at the time.

Patients with comorbid psychiatric disorders or drug use were excluded from the study.

Psychological distress was assessed at baseline, before randomization, and then annually for 5 years using the Impact of Rheumatic Diseases on General Health and Lifestyle (IRGL) questionnaire. The anxiety portion of IRGL consists of 10 items (scored from 10 to 40) derived from the Spielberger state–trait anxiety inventory; the depressed mood scale consists of six items (scored from 0 to 24).

Disease activity according to erythrocyte sedimentation rate (ESR) and the Thompson articular index was assessed at baseline, every 3 months for the first 2 years, and every 6 months for the next 3 years.

At baseline, the authors found that 45% of patients had a depressed mood according to the IRGL scale, while 36% had anxiety.

Also at baseline, the mean Thompson joint index was 146.0, while the mean ESR was 41.1 mm/hour.

Overall, these high levels of both disease activity and psychological distress decreased sharply in the first year, and continued to decrease over the course of the study, reported the authors, although 26% of patients still experienced depressed mood after 5 years and 23% reported anxiety.

However, looking prospectively, the authors found that scores exceeding zero on the depressed mood scale were associated with a higher Thompson joint score (P = .03) and a higher ESR (P = .04) 6 months later.

Similarly, a higher Thompson joint score was associated with higher levels of depressed mood (P = .03) and anxiety (P = .02) at assessments occurring 6 months afterward.

On the other hand, elevated anxiety scores were not associated with higher disease activity later on.

"Our data do not support the notion that psychological stress may cause disease flares," despite "weak" evidence that stress may exacerbate disease activity, they wrote.

Nor did elevated ESR levels predict psychological distress down the line.

The authors did admit to several weaknesses in their study. For one, "we used existing data with relatively long intervals between assessments," wrote Dr. Overman. "More frequent monitoring, for example, every 3 months during 5 years, will increase the chance of finding disease flares and substantial mood changes."

Additionally, ESR levels and the Thompson joint index are not the only measurements of disease activity available. The authors pointed out that their findings "do not generalize to cytokine and hypothalamic–pituitary–adrenal axis functioning," for example.

The authors disclosed no individual conflicts of interest in regard to this study, which was funded by grants from Utrecht University and the Dutch Arthritis Association.

Clinical trials in rheumatoid arthritis that have been done for drug approval fail to address numerous issues critically important to clinical care, according to an American College of Rheumatology task force report.

The group was critical of current clinical trial design and offered half a dozen recommendations for reforms aimed at boosting clinical relevance. The task force also drew up a ranked priority list for the next generation of RA clinical trials, i.e., studies needed to address current major knowledge gaps. Topping this must-have list are trials of induction therapy in early disease.

▸ Induction therapy. The group recommended as an initial practical step a three-armed trial comparing current standard conventional methotrexate monotherapy to methotrexate plus a tumor necrosis factor (TNF) inhibitor versus methotrexate plus a non-TNF inhibitor biologic agent. This trial should be double-blind and consist of three phases: induction, maintenance therapy, and treatment withdrawal in patients whose disease goes into remission. It was the strong consensus of the task force that such a trial holds the greatest potential for advancing clinical care.

Biologic specimens should routinely be collected during this and all the other next-generation clinical trials in an intensive effort to identify biomarkers that will allow rational selection of medications and the tapering of treatment without triggering relapse. The urgent need for such biomarkers was “a recurrent theme that prominently permeated and at times dominated our discussions,” according to the report of the task force chaired by Dr. James R. O'Dell, professor of medicine and chief of the section of rheumatology and immunology at the University of Nebraska, Omaha, who is also incoming president of the American College of Rheumatology.

In descending order of importance and urgency, the other topics on the task force's clinical trials priority list are:

▸ Treatment of disease that remains active despite methotrexate and a first anti-TNF biologic. The group believed that in an ideal world, a clinical trial addressing this scenario would continue background methotrexate while randomizing patients to a different TNF inhibitor, the T-cell mediator abatacept, the CD20-directed cytolytic antibody rituximab, or the interleukin-6 receptor blocker tocilizumab. That may be too big an undertaking to be practical. At the very least, the next generation of studies in this patient population ought to compare two biologics having different mechanisms, according to the task force report (Arthritis Rheum. 2011;63:2151-6 [doi:10.1002/art.30402]).

▸ Patients in remission while on treatment. At present there are essentially no data to guide medication tapering and discontinuation decisions. The panel proposed piggybacking tapering trials – with liberal collection of biologic specimens – on the back of current trials and next-generation induction trials.

▸ Active disease despite methotrexate therapy. Roughly 70% of patients with early RA fail to achieve low disease activity on methotrexate monotherapy. There is a need for clinical trials aimed at defining optimal methotrexate dosing strategies, the panel agreed. Beyond that, however, the task force was split on the best way forward. Some argued that active comparator trials of various add-on therapies in suboptimal responders to methotrexate are badly needed now, while others said it makes more sense to hold off until biomarkers can be identified that will help in making individualized treatment decisions based on an agent's mechanism of action.

The task force didn't address the issue of how the proposed research agenda will be funded. Of note, however, of 25 experts invited to an ACR conference on clinical trial priorities and design that was held last year, most were from academia, four came from the National Institutes of Health, three were Food and Drug Administration officials, and none were from the pharmaceutical industry.

The task force proposed numerous changes in clinical trial design aimed at yielding results that are more meaningful to clinical rheumatology practice. For example, the group declared that in the current era of proven highly effective RA therapies, placebo-controlled clinical trials have become ethically questionable and should be greatly de-emphasized in favor of active comparator studies. The task force also raised ethical concerns about the current rule that an assigned therapy must be continued for a prolonged period of follow-up, often 1-2 years, even though modern therapies are expected to bring maximum clinical benefit in 3-6 months.

The panel expressed reservations about the generalizability of clinical trials in RA that are increasingly being conducted in developing countries. The group recommended that when these trials are reported, the investigators should fully describe the study population and assess the generalizability of the findings.

In addition to Dr. O'Dell, the members of the ACR Rheumatoid Arthritis Clinical Trial Investigators Ad Hoc Task Force were co-chair Dr. Michael E. Weinblatt of Brigham and Women's Hospital, Boston; Dr. Ted R. Mikuls of the University of Nebraska, Omaha; and Dr. Robert A. Colbert of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Md. Dr. Weinblatt has received consulting fees from Abbott, Amgen, Astellas, Astra-Zeneca, Biogen Idec, Bristol-Myers Squibb, Centocor, Crescendo, Lilly, Pfizer, and Roche.

The need for such biomarkers was 'a recurrent theme that prominently permeated and at times dominated our discussions.'

Source DR. O'DELL

Clinical trials in rheumatoid arthritis that have been done for drug approval fail to address numerous issues critically important to clinical care, according to an American College of Rheumatology task force report.

The group was critical of current clinical trial design and offered half a dozen recommendations for reforms aimed at boosting clinical relevance. The task force also drew up a ranked priority list for the next generation of RA clinical trials, i.e., studies needed to address current major knowledge gaps. Topping this must-have list are trials of induction therapy in early disease.

▸ Induction therapy. The group recommended as an initial practical step a three-armed trial comparing current standard conventional methotrexate monotherapy to methotrexate plus a tumor necrosis factor (TNF) inhibitor versus methotrexate plus a non-TNF inhibitor biologic agent. This trial should be double-blind and consist of three phases: induction, maintenance therapy, and treatment withdrawal in patients whose disease goes into remission. It was the strong consensus of the task force that such a trial holds the greatest potential for advancing clinical care.

Biologic specimens should routinely be collected during this and all the other next-generation clinical trials in an intensive effort to identify biomarkers that will allow rational selection of medications and the tapering of treatment without triggering relapse. The urgent need for such biomarkers was “a recurrent theme that prominently permeated and at times dominated our discussions,” according to the report of the task force chaired by Dr. James R. O'Dell, professor of medicine and chief of the section of rheumatology and immunology at the University of Nebraska, Omaha, who is also incoming president of the American College of Rheumatology.

In descending order of importance and urgency, the other topics on the task force's clinical trials priority list are:

▸ Treatment of disease that remains active despite methotrexate and a first anti-TNF biologic. The group believed that in an ideal world, a clinical trial addressing this scenario would continue background methotrexate while randomizing patients to a different TNF inhibitor, the T-cell mediator abatacept, the CD20-directed cytolytic antibody rituximab, or the interleukin-6 receptor blocker tocilizumab. That may be too big an undertaking to be practical. At the very least, the next generation of studies in this patient population ought to compare two biologics having different mechanisms, according to the task force report (Arthritis Rheum. 2011;63:2151-6 [doi:10.1002/art.30402]).

▸ Patients in remission while on treatment. At present there are essentially no data to guide medication tapering and discontinuation decisions. The panel proposed piggybacking tapering trials – with liberal collection of biologic specimens – on the back of current trials and next-generation induction trials.

▸ Active disease despite methotrexate therapy. Roughly 70% of patients with early RA fail to achieve low disease activity on methotrexate monotherapy. There is a need for clinical trials aimed at defining optimal methotrexate dosing strategies, the panel agreed. Beyond that, however, the task force was split on the best way forward. Some argued that active comparator trials of various add-on therapies in suboptimal responders to methotrexate are badly needed now, while others said it makes more sense to hold off until biomarkers can be identified that will help in making individualized treatment decisions based on an agent's mechanism of action.

The task force didn't address the issue of how the proposed research agenda will be funded. Of note, however, of 25 experts invited to an ACR conference on clinical trial priorities and design that was held last year, most were from academia, four came from the National Institutes of Health, three were Food and Drug Administration officials, and none were from the pharmaceutical industry.

The task force proposed numerous changes in clinical trial design aimed at yielding results that are more meaningful to clinical rheumatology practice. For example, the group declared that in the current era of proven highly effective RA therapies, placebo-controlled clinical trials have become ethically questionable and should be greatly de-emphasized in favor of active comparator studies. The task force also raised ethical concerns about the current rule that an assigned therapy must be continued for a prolonged period of follow-up, often 1-2 years, even though modern therapies are expected to bring maximum clinical benefit in 3-6 months.

The panel expressed reservations about the generalizability of clinical trials in RA that are increasingly being conducted in developing countries. The group recommended that when these trials are reported, the investigators should fully describe the study population and assess the generalizability of the findings.

In addition to Dr. O'Dell, the members of the ACR Rheumatoid Arthritis Clinical Trial Investigators Ad Hoc Task Force were co-chair Dr. Michael E. Weinblatt of Brigham and Women's Hospital, Boston; Dr. Ted R. Mikuls of the University of Nebraska, Omaha; and Dr. Robert A. Colbert of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Md. Dr. Weinblatt has received consulting fees from Abbott, Amgen, Astellas, Astra-Zeneca, Biogen Idec, Bristol-Myers Squibb, Centocor, Crescendo, Lilly, Pfizer, and Roche.

The need for such biomarkers was 'a recurrent theme that prominently permeated and at times dominated our discussions.'

Source DR. O'DELL

Clinical trials in rheumatoid arthritis that have been done for drug approval fail to address numerous issues critically important to clinical care, according to an American College of Rheumatology task force report.

The group was critical of current clinical trial design and offered half a dozen recommendations for reforms aimed at boosting clinical relevance. The task force also drew up a ranked priority list for the next generation of RA clinical trials, i.e., studies needed to address current major knowledge gaps. Topping this must-have list are trials of induction therapy in early disease.

▸ Induction therapy. The group recommended as an initial practical step a three-armed trial comparing current standard conventional methotrexate monotherapy to methotrexate plus a tumor necrosis factor (TNF) inhibitor versus methotrexate plus a non-TNF inhibitor biologic agent. This trial should be double-blind and consist of three phases: induction, maintenance therapy, and treatment withdrawal in patients whose disease goes into remission. It was the strong consensus of the task force that such a trial holds the greatest potential for advancing clinical care.

Biologic specimens should routinely be collected during this and all the other next-generation clinical trials in an intensive effort to identify biomarkers that will allow rational selection of medications and the tapering of treatment without triggering relapse. The urgent need for such biomarkers was “a recurrent theme that prominently permeated and at times dominated our discussions,” according to the report of the task force chaired by Dr. James R. O'Dell, professor of medicine and chief of the section of rheumatology and immunology at the University of Nebraska, Omaha, who is also incoming president of the American College of Rheumatology.

In descending order of importance and urgency, the other topics on the task force's clinical trials priority list are:

▸ Treatment of disease that remains active despite methotrexate and a first anti-TNF biologic. The group believed that in an ideal world, a clinical trial addressing this scenario would continue background methotrexate while randomizing patients to a different TNF inhibitor, the T-cell mediator abatacept, the CD20-directed cytolytic antibody rituximab, or the interleukin-6 receptor blocker tocilizumab. That may be too big an undertaking to be practical. At the very least, the next generation of studies in this patient population ought to compare two biologics having different mechanisms, according to the task force report (Arthritis Rheum. 2011;63:2151-6 [doi:10.1002/art.30402]).

▸ Patients in remission while on treatment. At present there are essentially no data to guide medication tapering and discontinuation decisions. The panel proposed piggybacking tapering trials – with liberal collection of biologic specimens – on the back of current trials and next-generation induction trials.

▸ Active disease despite methotrexate therapy. Roughly 70% of patients with early RA fail to achieve low disease activity on methotrexate monotherapy. There is a need for clinical trials aimed at defining optimal methotrexate dosing strategies, the panel agreed. Beyond that, however, the task force was split on the best way forward. Some argued that active comparator trials of various add-on therapies in suboptimal responders to methotrexate are badly needed now, while others said it makes more sense to hold off until biomarkers can be identified that will help in making individualized treatment decisions based on an agent's mechanism of action.

The task force didn't address the issue of how the proposed research agenda will be funded. Of note, however, of 25 experts invited to an ACR conference on clinical trial priorities and design that was held last year, most were from academia, four came from the National Institutes of Health, three were Food and Drug Administration officials, and none were from the pharmaceutical industry.

The task force proposed numerous changes in clinical trial design aimed at yielding results that are more meaningful to clinical rheumatology practice. For example, the group declared that in the current era of proven highly effective RA therapies, placebo-controlled clinical trials have become ethically questionable and should be greatly de-emphasized in favor of active comparator studies. The task force also raised ethical concerns about the current rule that an assigned therapy must be continued for a prolonged period of follow-up, often 1-2 years, even though modern therapies are expected to bring maximum clinical benefit in 3-6 months.

The panel expressed reservations about the generalizability of clinical trials in RA that are increasingly being conducted in developing countries. The group recommended that when these trials are reported, the investigators should fully describe the study population and assess the generalizability of the findings.

In addition to Dr. O'Dell, the members of the ACR Rheumatoid Arthritis Clinical Trial Investigators Ad Hoc Task Force were co-chair Dr. Michael E. Weinblatt of Brigham and Women's Hospital, Boston; Dr. Ted R. Mikuls of the University of Nebraska, Omaha; and Dr. Robert A. Colbert of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, Md. Dr. Weinblatt has received consulting fees from Abbott, Amgen, Astellas, Astra-Zeneca, Biogen Idec, Bristol-Myers Squibb, Centocor, Crescendo, Lilly, Pfizer, and Roche.

The need for such biomarkers was 'a recurrent theme that prominently permeated and at times dominated our discussions.'

Source DR. O'DELL

Major Finding: Incorporating MRI bone edema findings, together with clinical and biochemical parameters, yielded a prediction model that had a sensitivity of 81% and a specificity of 82% for progression to RA.

Data Source: The study involved 24 healthy controls and 116 patients with early undifferentiated arthritis, 23% of whom went on to meet American College of Rheumatology 1987 criteria for RA during a median 17 months of follow-up.

Disclosures: This study was funded by the Danish Rheumatism Foundation and other foundation grants. While Dr. Duer-Jensen reported having no financial conflicts of interest, several of her associates did. Those can be found on the full text of the journal article.

Magnetic resonance imaging evidence of bone edema in the wrist and metatarsophalangeal joints was an independent predictor of future development of rheumatoid arthritis in a prospective Danish study of patients with early undifferentiated arthritis.

Incorporating MRI bone edema findings, together with clinical and biochemical parameters, yielded a prediction model that showed unprecedented accuracy in identifying which patients would or would not develop rheumatoid arthritis, Dr. Anne Duer-Jensen of Copenhagen University Hospital at Hvidovre and Copenhagen University Hospital at Glostrup, and her associates reported in Arthritis & Rheumatism (2011;63:2192-202).

The study involved 116 patients with early undifferentiated arthritis, 23% of whom went on to meet American College of Rheumatology 1987 criteria for RA during a median 17 months of follow-up. They were matched with 24 healthy controls. The predictive model had a sensitivity of 81% and a specificity of 82% for progression to RA. Thus, it classified 82% of patients correctly.

That's a markedly better predictive accuracy than achieved when the investigators applied the published and validated van der Helm-van Mil prediction model to the same study population. The van der Helm-van Mil model (Arthritis Rheum. 2007;56:433-40) had a 60% predictive accuracy.

Participants in the Danish study had two or more tender joints and/or two or more swollen joints among the wrist, metatarsophalangeal (MTP), proximal interphalangeal, or metacarpophalangeal joints for more than 6 weeks but less than 2 years. None of the 116 subjects had a specific rheumatologic diagnosis at baseline. Thus, they were typical of the patients often referred to rheumatologists for early undifferentiated arthritis, a condition that can morph into osteoarthritis, RA, persistent arthralgias, or nonprogressive disease.

The investigators developed their predictive model based on the findings of a multivariate logistic regression analysis that encompassed numerous variables. The final prediction model included four independent predictors of RA: serum positivity for rheumatoid factor, the presence of hand arthritis, morning stiffness lasting longer than 1 hour, and the MRI summary score for bone edema in the wrist and MTP joints that grew out of the Outcome Measures in Rheumatology Clinical Trials, or OMERACT (J. Rheumatol. 2003;30:1385-6).

Of note, in the Danish study the presence of rheumatoid factor was an independent predictor of subsequent RA, whereas a positive anti–cyclic citrullinated peptide test was not, unlike in several recent studies.

MRI summary scores for bone edema proved to be a significantly more potent predictor of RA than MRI scores for synovitis or erosion.

The formula for the current iteration of the prediction model is cumbersome. A simpler version would be welcome.

Toward that end, the investigators tried using MRI bone edema scores for the wrist or MTP joints alone, but they found that it unacceptably weakened the model's predictive power.

The next step in this project will be to see how the prediction model performs in other cohorts of patients with early undifferentiated arthritis.

The goal is to develop a tool that enables physicians to extend the current, highly successful early and aggressive treatment strategy for RA into the pre-RA setting.

Major Finding: Incorporating MRI bone edema findings, together with clinical and biochemical parameters, yielded a prediction model that had a sensitivity of 81% and a specificity of 82% for progression to RA.

Data Source: The study involved 24 healthy controls and 116 patients with early undifferentiated arthritis, 23% of whom went on to meet American College of Rheumatology 1987 criteria for RA during a median 17 months of follow-up.

Disclosures: This study was funded by the Danish Rheumatism Foundation and other foundation grants. While Dr. Duer-Jensen reported having no financial conflicts of interest, several of her associates did. Those can be found on the full text of the journal article.

Magnetic resonance imaging evidence of bone edema in the wrist and metatarsophalangeal joints was an independent predictor of future development of rheumatoid arthritis in a prospective Danish study of patients with early undifferentiated arthritis.

Incorporating MRI bone edema findings, together with clinical and biochemical parameters, yielded a prediction model that showed unprecedented accuracy in identifying which patients would or would not develop rheumatoid arthritis, Dr. Anne Duer-Jensen of Copenhagen University Hospital at Hvidovre and Copenhagen University Hospital at Glostrup, and her associates reported in Arthritis & Rheumatism (2011;63:2192-202).

The study involved 116 patients with early undifferentiated arthritis, 23% of whom went on to meet American College of Rheumatology 1987 criteria for RA during a median 17 months of follow-up. They were matched with 24 healthy controls. The predictive model had a sensitivity of 81% and a specificity of 82% for progression to RA. Thus, it classified 82% of patients correctly.

That's a markedly better predictive accuracy than achieved when the investigators applied the published and validated van der Helm-van Mil prediction model to the same study population. The van der Helm-van Mil model (Arthritis Rheum. 2007;56:433-40) had a 60% predictive accuracy.

Participants in the Danish study had two or more tender joints and/or two or more swollen joints among the wrist, metatarsophalangeal (MTP), proximal interphalangeal, or metacarpophalangeal joints for more than 6 weeks but less than 2 years. None of the 116 subjects had a specific rheumatologic diagnosis at baseline. Thus, they were typical of the patients often referred to rheumatologists for early undifferentiated arthritis, a condition that can morph into osteoarthritis, RA, persistent arthralgias, or nonprogressive disease.

The investigators developed their predictive model based on the findings of a multivariate logistic regression analysis that encompassed numerous variables. The final prediction model included four independent predictors of RA: serum positivity for rheumatoid factor, the presence of hand arthritis, morning stiffness lasting longer than 1 hour, and the MRI summary score for bone edema in the wrist and MTP joints that grew out of the Outcome Measures in Rheumatology Clinical Trials, or OMERACT (J. Rheumatol. 2003;30:1385-6).

Of note, in the Danish study the presence of rheumatoid factor was an independent predictor of subsequent RA, whereas a positive anti–cyclic citrullinated peptide test was not, unlike in several recent studies.

MRI summary scores for bone edema proved to be a significantly more potent predictor of RA than MRI scores for synovitis or erosion.

The formula for the current iteration of the prediction model is cumbersome. A simpler version would be welcome.

Toward that end, the investigators tried using MRI bone edema scores for the wrist or MTP joints alone, but they found that it unacceptably weakened the model's predictive power.

The next step in this project will be to see how the prediction model performs in other cohorts of patients with early undifferentiated arthritis.

The goal is to develop a tool that enables physicians to extend the current, highly successful early and aggressive treatment strategy for RA into the pre-RA setting.

Major Finding: Incorporating MRI bone edema findings, together with clinical and biochemical parameters, yielded a prediction model that had a sensitivity of 81% and a specificity of 82% for progression to RA.

Data Source: The study involved 24 healthy controls and 116 patients with early undifferentiated arthritis, 23% of whom went on to meet American College of Rheumatology 1987 criteria for RA during a median 17 months of follow-up.

Disclosures: This study was funded by the Danish Rheumatism Foundation and other foundation grants. While Dr. Duer-Jensen reported having no financial conflicts of interest, several of her associates did. Those can be found on the full text of the journal article.

Magnetic resonance imaging evidence of bone edema in the wrist and metatarsophalangeal joints was an independent predictor of future development of rheumatoid arthritis in a prospective Danish study of patients with early undifferentiated arthritis.

Incorporating MRI bone edema findings, together with clinical and biochemical parameters, yielded a prediction model that showed unprecedented accuracy in identifying which patients would or would not develop rheumatoid arthritis, Dr. Anne Duer-Jensen of Copenhagen University Hospital at Hvidovre and Copenhagen University Hospital at Glostrup, and her associates reported in Arthritis & Rheumatism (2011;63:2192-202).

The study involved 116 patients with early undifferentiated arthritis, 23% of whom went on to meet American College of Rheumatology 1987 criteria for RA during a median 17 months of follow-up. They were matched with 24 healthy controls. The predictive model had a sensitivity of 81% and a specificity of 82% for progression to RA. Thus, it classified 82% of patients correctly.

That's a markedly better predictive accuracy than achieved when the investigators applied the published and validated van der Helm-van Mil prediction model to the same study population. The van der Helm-van Mil model (Arthritis Rheum. 2007;56:433-40) had a 60% predictive accuracy.

Participants in the Danish study had two or more tender joints and/or two or more swollen joints among the wrist, metatarsophalangeal (MTP), proximal interphalangeal, or metacarpophalangeal joints for more than 6 weeks but less than 2 years. None of the 116 subjects had a specific rheumatologic diagnosis at baseline. Thus, they were typical of the patients often referred to rheumatologists for early undifferentiated arthritis, a condition that can morph into osteoarthritis, RA, persistent arthralgias, or nonprogressive disease.

The investigators developed their predictive model based on the findings of a multivariate logistic regression analysis that encompassed numerous variables. The final prediction model included four independent predictors of RA: serum positivity for rheumatoid factor, the presence of hand arthritis, morning stiffness lasting longer than 1 hour, and the MRI summary score for bone edema in the wrist and MTP joints that grew out of the Outcome Measures in Rheumatology Clinical Trials, or OMERACT (J. Rheumatol. 2003;30:1385-6).

Of note, in the Danish study the presence of rheumatoid factor was an independent predictor of subsequent RA, whereas a positive anti–cyclic citrullinated peptide test was not, unlike in several recent studies.

MRI summary scores for bone edema proved to be a significantly more potent predictor of RA than MRI scores for synovitis or erosion.

The formula for the current iteration of the prediction model is cumbersome. A simpler version would be welcome.

Toward that end, the investigators tried using MRI bone edema scores for the wrist or MTP joints alone, but they found that it unacceptably weakened the model's predictive power.

The next step in this project will be to see how the prediction model performs in other cohorts of patients with early undifferentiated arthritis.

The goal is to develop a tool that enables physicians to extend the current, highly successful early and aggressive treatment strategy for RA into the pre-RA setting.

The use of oral contraceptives before or at the time of symptom onset in women with inflammatory polyarthritis appears to confer long-term benefits in functional outcome.

In the largest-ever prospective study of the relationship between oral contraceptives and disease outcome, data from the Norfolk (U.K.) Arthritis Register showed that OC use prior to symptom onset was associated with a 35% reduction in median Health Assessment Questionnaire (HAQ) scores at 5 years of follow-up, compared with women who hadn't taken OCs beforehand.

Moreover, the benefit of taking OCs around the time of symptom onset was even greater. Women on OCs at symptom onset had a 21% lower median HAQ score at 5 years, after adjustment for age, parity, and other potential confounders, than women who weren't taking OCs at symptom onset but had previously done so.

OC use during follow-up was also associated with lower HAQ scores, but this finding reached significance only for the subset of women with moderate or severe functional disability at their previous assessment.

The study involved 523 users and 140 nonusers of OCs prior to onset of inflammatory polyarthritis, along with 73 OC users and 192 nonusers at symptom onset, and 95 users and 170 nonusers during follow-up, which lasted a median of 4.9 years. The median score on the HAQ, a validated measure of functional ability, was 1.0 on a 0-3 scale at symptom onset, indicative of moderate disability, Dr. Deborah P.M. Symmons and her coworkers reported in Arthritis & Rheumatism (2011;63:2183-91).

Although the Norfolk Arthritis Register is open to patients with inflammatory polyarthritis, it has previously been established that 75% of enrollees meet American College of Rheumatology diagnostic criteria for rheumatoid arthritis within 5 years of symptom onset.

The investigators offered two potential mechanisms to explain the observed relationship between OC use and disease outcome. One possibility is that the hormonal environment fostered by OCs results in an increase in heat-shock proteins, resulting in an immunotolerant state that reduces rheumatoid arthritis symptoms. Another potential mechanism is that the artificial luteal phase induced by combined estrogen/progesterone OCs tempers rheumatoid arthritis symptoms; this is consistent with an earlier report by other investigators that rheumatoid arthritis symptoms in 14 women were significantly reduced just after ovulation, wrote Dr. Symmons, a professor of rheumatology and musculoskeletal epidemiology at the University of Manchester (England), and her colleagues.

The Norfolk Arthritis Register is funded by Arthritis Research UK. Dr. Symmons and her coinvestigators reported having no financial conflicts.

The use of oral contraceptives before or at the time of symptom onset in women with inflammatory polyarthritis appears to confer long-term benefits in functional outcome.

In the largest-ever prospective study of the relationship between oral contraceptives and disease outcome, data from the Norfolk (U.K.) Arthritis Register showed that OC use prior to symptom onset was associated with a 35% reduction in median Health Assessment Questionnaire (HAQ) scores at 5 years of follow-up, compared with women who hadn't taken OCs beforehand.

Moreover, the benefit of taking OCs around the time of symptom onset was even greater. Women on OCs at symptom onset had a 21% lower median HAQ score at 5 years, after adjustment for age, parity, and other potential confounders, than women who weren't taking OCs at symptom onset but had previously done so.

OC use during follow-up was also associated with lower HAQ scores, but this finding reached significance only for the subset of women with moderate or severe functional disability at their previous assessment.

The study involved 523 users and 140 nonusers of OCs prior to onset of inflammatory polyarthritis, along with 73 OC users and 192 nonusers at symptom onset, and 95 users and 170 nonusers during follow-up, which lasted a median of 4.9 years. The median score on the HAQ, a validated measure of functional ability, was 1.0 on a 0-3 scale at symptom onset, indicative of moderate disability, Dr. Deborah P.M. Symmons and her coworkers reported in Arthritis & Rheumatism (2011;63:2183-91).

Although the Norfolk Arthritis Register is open to patients with inflammatory polyarthritis, it has previously been established that 75% of enrollees meet American College of Rheumatology diagnostic criteria for rheumatoid arthritis within 5 years of symptom onset.

The investigators offered two potential mechanisms to explain the observed relationship between OC use and disease outcome. One possibility is that the hormonal environment fostered by OCs results in an increase in heat-shock proteins, resulting in an immunotolerant state that reduces rheumatoid arthritis symptoms. Another potential mechanism is that the artificial luteal phase induced by combined estrogen/progesterone OCs tempers rheumatoid arthritis symptoms; this is consistent with an earlier report by other investigators that rheumatoid arthritis symptoms in 14 women were significantly reduced just after ovulation, wrote Dr. Symmons, a professor of rheumatology and musculoskeletal epidemiology at the University of Manchester (England), and her colleagues.

The Norfolk Arthritis Register is funded by Arthritis Research UK. Dr. Symmons and her coinvestigators reported having no financial conflicts.

The use of oral contraceptives before or at the time of symptom onset in women with inflammatory polyarthritis appears to confer long-term benefits in functional outcome.

In the largest-ever prospective study of the relationship between oral contraceptives and disease outcome, data from the Norfolk (U.K.) Arthritis Register showed that OC use prior to symptom onset was associated with a 35% reduction in median Health Assessment Questionnaire (HAQ) scores at 5 years of follow-up, compared with women who hadn't taken OCs beforehand.

Moreover, the benefit of taking OCs around the time of symptom onset was even greater. Women on OCs at symptom onset had a 21% lower median HAQ score at 5 years, after adjustment for age, parity, and other potential confounders, than women who weren't taking OCs at symptom onset but had previously done so.

OC use during follow-up was also associated with lower HAQ scores, but this finding reached significance only for the subset of women with moderate or severe functional disability at their previous assessment.

The study involved 523 users and 140 nonusers of OCs prior to onset of inflammatory polyarthritis, along with 73 OC users and 192 nonusers at symptom onset, and 95 users and 170 nonusers during follow-up, which lasted a median of 4.9 years. The median score on the HAQ, a validated measure of functional ability, was 1.0 on a 0-3 scale at symptom onset, indicative of moderate disability, Dr. Deborah P.M. Symmons and her coworkers reported in Arthritis & Rheumatism (2011;63:2183-91).

Although the Norfolk Arthritis Register is open to patients with inflammatory polyarthritis, it has previously been established that 75% of enrollees meet American College of Rheumatology diagnostic criteria for rheumatoid arthritis within 5 years of symptom onset.

The investigators offered two potential mechanisms to explain the observed relationship between OC use and disease outcome. One possibility is that the hormonal environment fostered by OCs results in an increase in heat-shock proteins, resulting in an immunotolerant state that reduces rheumatoid arthritis symptoms. Another potential mechanism is that the artificial luteal phase induced by combined estrogen/progesterone OCs tempers rheumatoid arthritis symptoms; this is consistent with an earlier report by other investigators that rheumatoid arthritis symptoms in 14 women were significantly reduced just after ovulation, wrote Dr. Symmons, a professor of rheumatology and musculoskeletal epidemiology at the University of Manchester (England), and her colleagues.

The Norfolk Arthritis Register is funded by Arthritis Research UK. Dr. Symmons and her coinvestigators reported having no financial conflicts.