Anti-TNFs in Pregnancy Study Advises Continued Caution

What I Tell My Patients
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Anti-TNFs in Pregnancy Study Advises Continued Caution

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, is from the "largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy" to date, according to the authors.

Despite its relatively large size, however, the study was unable to control for the looming possibility that disease severity itself plays a role in adverse pregnancy outcomes, as the authors readily admitted.

Nevertheless, "no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain," recommended the authors.

The study was led by Dr. Suzanne M. M. Verstappen of the University of Manchester’s Arthritis Research UK Epidemiology Unit and was published online in Annals of the Rheumatic Diseases.

Dr. Verstappen and her colleagues looked at women in the registry who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs, two drugs with a "known risk of adverse pregnancy outcomes," according to the authors.

A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822]).

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb).

Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post-20 weeks).

There was also one neonatal death registered.

The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death.

Finally, among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

In all cohorts, the majority of patients had RA, and the majority took etanercept.

The baseline disease activity score-28 (DAS28) was significantly higher in the anti-TNF cohorts, vs. cohort III: 6.5, 6.1, and 6.0 in cohorts Ia, Ib, and II, respectively, vs. 5.1 in cohort III.

Dr. H. Michael Belmont, medical director of New York University’s Hospital for Joint Diseases, as well as the director of the lupus clinic at Bellevue Hospital, New York, commented that, until more data are available, "The default choice would be to avoid these drugs during pregnancy. Certainly starting their use in a women contemplating conception should be delayed based on the data on hand."

Dr. Belmont, who was not affiliated with this study, joined the authors in pointing to a 2009 study by Carter et al., which found an increased observed: expected incidence of VACTERL defects (vertebral abnormalities, anal atresia, and/or cardiac, trachea, esophageal, renal, and limb abnormalities) in children born to women taking anti-TNFs (J. Rheumatol. 2009;36:635-41).

However, "The total observed number [of children born with VACTERL abnormalities] was small, 19 newborns, and the actual rate could not be calculated, as the authors relied on the [Food & Drug Administration] base of adverse events but did not know the [actual] number of exposed pregnancies, having to rely instead on historical controls to determine the expected ratio," he conceded.

On the other hand, Dr. Arthur Kavanaugh, a rheumatologist and director of the at the University of California San Diego’s Center for Innovative Therapy pointed to flaws in the current study’s analysis.

"The other explanation [for the finding of increased spontaneous abortion among anti-TNF users] is that it’s the disease more than the drug, so that people who have worse RA are going to have pregnancy outcomes that are not necessarily as good, and you just don’t know that from this because there’s only 10 people in the DMARD-only arm," he said in an interview.

"That’s just incredibly small. If you have one different outcome in that group, it would make a humongous difference in how you look at the data."

 

 

He added: "You can’t ignore the disease, and it’s the disease itself that’s going to affect the outcome as well."

Dr. Kavanaugh, like Dr. Belmont, was not affiliated with the study.

The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. They added that they had no personal competing interests in relation to this study.

Dr. Kavanaugh disclosed that he has done research for the makers of TNF inhibitors, including Abbot Laboratories, Amgen, Centocor, and UCB. Dr. Belmont did not make any disclosures relevant to this study.

The British Society for Rheumatology receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

Body

The only way to definitively address the question of risk associated with anti-TNFs and pregnancy would be to conduct a randomized controlled trial, according to Dr. Deborah P. M. Symmons.

There are, however, a few problems with that strategy. "Clearly, this would be very difficult to design, would need to be very large, and is never going to happen!" she joked.

"Beyond that, we have to wait for anecdotal evidence to accumulate."

In the meantime, she said, "We advise all patients with rheumatoid arthritis to discuss a planned pregnancy with their rheumatologist prior to conception in order to make prospective plans about what to do about treatment.

"There are a number of other antirheumatic drugs, for example methotrexate and leflunomide, which carry a substantially higher risk than has been seen with anti-TNF therapy so far. However, many patients on anti-TNFs take them with another anti-rheumatic drug."

According to Dr. Symmons, when treating a female patient of child-bearing age, "I would share what is currently known about the risks and benefits of continuing anti-TNF therapy with the woman with RA and let her ask further questions and make up her own mind about what to do.

"This study is reassuring for us to continue our current practice."

Dr. Symmons is one of the authors of the current study as well as a professor of rheumatology and musculoskeletal epidemiology at the University of Manchester, in the UK. She had no financial interests to disclose.

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The only way to definitively address the question of risk associated with anti-TNFs and pregnancy would be to conduct a randomized controlled trial, according to Dr. Deborah P. M. Symmons.

There are, however, a few problems with that strategy. "Clearly, this would be very difficult to design, would need to be very large, and is never going to happen!" she joked.

"Beyond that, we have to wait for anecdotal evidence to accumulate."

In the meantime, she said, "We advise all patients with rheumatoid arthritis to discuss a planned pregnancy with their rheumatologist prior to conception in order to make prospective plans about what to do about treatment.

"There are a number of other antirheumatic drugs, for example methotrexate and leflunomide, which carry a substantially higher risk than has been seen with anti-TNF therapy so far. However, many patients on anti-TNFs take them with another anti-rheumatic drug."

According to Dr. Symmons, when treating a female patient of child-bearing age, "I would share what is currently known about the risks and benefits of continuing anti-TNF therapy with the woman with RA and let her ask further questions and make up her own mind about what to do.

"This study is reassuring for us to continue our current practice."

Dr. Symmons is one of the authors of the current study as well as a professor of rheumatology and musculoskeletal epidemiology at the University of Manchester, in the UK. She had no financial interests to disclose.

Body

The only way to definitively address the question of risk associated with anti-TNFs and pregnancy would be to conduct a randomized controlled trial, according to Dr. Deborah P. M. Symmons.

There are, however, a few problems with that strategy. "Clearly, this would be very difficult to design, would need to be very large, and is never going to happen!" she joked.

"Beyond that, we have to wait for anecdotal evidence to accumulate."

In the meantime, she said, "We advise all patients with rheumatoid arthritis to discuss a planned pregnancy with their rheumatologist prior to conception in order to make prospective plans about what to do about treatment.

"There are a number of other antirheumatic drugs, for example methotrexate and leflunomide, which carry a substantially higher risk than has been seen with anti-TNF therapy so far. However, many patients on anti-TNFs take them with another anti-rheumatic drug."

According to Dr. Symmons, when treating a female patient of child-bearing age, "I would share what is currently known about the risks and benefits of continuing anti-TNF therapy with the woman with RA and let her ask further questions and make up her own mind about what to do.

"This study is reassuring for us to continue our current practice."

Dr. Symmons is one of the authors of the current study as well as a professor of rheumatology and musculoskeletal epidemiology at the University of Manchester, in the UK. She had no financial interests to disclose.

Title
What I Tell My Patients
What I Tell My Patients

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, is from the "largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy" to date, according to the authors.

Despite its relatively large size, however, the study was unable to control for the looming possibility that disease severity itself plays a role in adverse pregnancy outcomes, as the authors readily admitted.

Nevertheless, "no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain," recommended the authors.

The study was led by Dr. Suzanne M. M. Verstappen of the University of Manchester’s Arthritis Research UK Epidemiology Unit and was published online in Annals of the Rheumatic Diseases.

Dr. Verstappen and her colleagues looked at women in the registry who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs, two drugs with a "known risk of adverse pregnancy outcomes," according to the authors.

A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822]).

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb).

Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post-20 weeks).

There was also one neonatal death registered.

The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death.

Finally, among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

In all cohorts, the majority of patients had RA, and the majority took etanercept.

The baseline disease activity score-28 (DAS28) was significantly higher in the anti-TNF cohorts, vs. cohort III: 6.5, 6.1, and 6.0 in cohorts Ia, Ib, and II, respectively, vs. 5.1 in cohort III.

Dr. H. Michael Belmont, medical director of New York University’s Hospital for Joint Diseases, as well as the director of the lupus clinic at Bellevue Hospital, New York, commented that, until more data are available, "The default choice would be to avoid these drugs during pregnancy. Certainly starting their use in a women contemplating conception should be delayed based on the data on hand."

Dr. Belmont, who was not affiliated with this study, joined the authors in pointing to a 2009 study by Carter et al., which found an increased observed: expected incidence of VACTERL defects (vertebral abnormalities, anal atresia, and/or cardiac, trachea, esophageal, renal, and limb abnormalities) in children born to women taking anti-TNFs (J. Rheumatol. 2009;36:635-41).

However, "The total observed number [of children born with VACTERL abnormalities] was small, 19 newborns, and the actual rate could not be calculated, as the authors relied on the [Food & Drug Administration] base of adverse events but did not know the [actual] number of exposed pregnancies, having to rely instead on historical controls to determine the expected ratio," he conceded.

On the other hand, Dr. Arthur Kavanaugh, a rheumatologist and director of the at the University of California San Diego’s Center for Innovative Therapy pointed to flaws in the current study’s analysis.

"The other explanation [for the finding of increased spontaneous abortion among anti-TNF users] is that it’s the disease more than the drug, so that people who have worse RA are going to have pregnancy outcomes that are not necessarily as good, and you just don’t know that from this because there’s only 10 people in the DMARD-only arm," he said in an interview.

"That’s just incredibly small. If you have one different outcome in that group, it would make a humongous difference in how you look at the data."

 

 

He added: "You can’t ignore the disease, and it’s the disease itself that’s going to affect the outcome as well."

Dr. Kavanaugh, like Dr. Belmont, was not affiliated with the study.

The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. They added that they had no personal competing interests in relation to this study.

Dr. Kavanaugh disclosed that he has done research for the makers of TNF inhibitors, including Abbot Laboratories, Amgen, Centocor, and UCB. Dr. Belmont did not make any disclosures relevant to this study.

The British Society for Rheumatology receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, is from the "largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy" to date, according to the authors.

Despite its relatively large size, however, the study was unable to control for the looming possibility that disease severity itself plays a role in adverse pregnancy outcomes, as the authors readily admitted.

Nevertheless, "no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain," recommended the authors.

The study was led by Dr. Suzanne M. M. Verstappen of the University of Manchester’s Arthritis Research UK Epidemiology Unit and was published online in Annals of the Rheumatic Diseases.

Dr. Verstappen and her colleagues looked at women in the registry who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs, two drugs with a "known risk of adverse pregnancy outcomes," according to the authors.

A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822]).

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb).

Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post-20 weeks).

There was also one neonatal death registered.

The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death.

Finally, among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

In all cohorts, the majority of patients had RA, and the majority took etanercept.

The baseline disease activity score-28 (DAS28) was significantly higher in the anti-TNF cohorts, vs. cohort III: 6.5, 6.1, and 6.0 in cohorts Ia, Ib, and II, respectively, vs. 5.1 in cohort III.

Dr. H. Michael Belmont, medical director of New York University’s Hospital for Joint Diseases, as well as the director of the lupus clinic at Bellevue Hospital, New York, commented that, until more data are available, "The default choice would be to avoid these drugs during pregnancy. Certainly starting their use in a women contemplating conception should be delayed based on the data on hand."

Dr. Belmont, who was not affiliated with this study, joined the authors in pointing to a 2009 study by Carter et al., which found an increased observed: expected incidence of VACTERL defects (vertebral abnormalities, anal atresia, and/or cardiac, trachea, esophageal, renal, and limb abnormalities) in children born to women taking anti-TNFs (J. Rheumatol. 2009;36:635-41).

However, "The total observed number [of children born with VACTERL abnormalities] was small, 19 newborns, and the actual rate could not be calculated, as the authors relied on the [Food & Drug Administration] base of adverse events but did not know the [actual] number of exposed pregnancies, having to rely instead on historical controls to determine the expected ratio," he conceded.

On the other hand, Dr. Arthur Kavanaugh, a rheumatologist and director of the at the University of California San Diego’s Center for Innovative Therapy pointed to flaws in the current study’s analysis.

"The other explanation [for the finding of increased spontaneous abortion among anti-TNF users] is that it’s the disease more than the drug, so that people who have worse RA are going to have pregnancy outcomes that are not necessarily as good, and you just don’t know that from this because there’s only 10 people in the DMARD-only arm," he said in an interview.

"That’s just incredibly small. If you have one different outcome in that group, it would make a humongous difference in how you look at the data."

 

 

He added: "You can’t ignore the disease, and it’s the disease itself that’s going to affect the outcome as well."

Dr. Kavanaugh, like Dr. Belmont, was not affiliated with the study.

The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. They added that they had no personal competing interests in relation to this study.

Dr. Kavanaugh disclosed that he has done research for the makers of TNF inhibitors, including Abbot Laboratories, Amgen, Centocor, and UCB. Dr. Belmont did not make any disclosures relevant to this study.

The British Society for Rheumatology receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

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Major Finding: Among women who took anti–tumor necrosis factor drugs at the time of conception, 24% of pregnancies ended in spontaneous abortion vs. 17% among women who took the drugs in the past but not at conception and 10% among women with no history of exposure.

Data Source: The British Society for Rheumatology Biologics Registry.

Disclosures: The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Roche, and Wyeth Pharmaceuticals. They added that they had no personal competing interests in relation to this study.

Dr. Kavanaugh disclosed that he has done research for the makers of TNF-inhibitors, including Abbot Laboratories, Amgen, Centocor, and UCB. Dr. Belmont did not make any disclosures relevant to this study.

The British Society for Rheumatology receives funding from several pharmaceutical companies, including the makers of anti-TNFS.

New Recommendations Outline Nurses' Role in Arthritis Care

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The role of the nurse in rheumatology varies widely among countries, in large part because of differences in legal regulations, as well as nurses’ educational background and funding issues related to overall health care provision.

However, a new set of recommendations aims to standardize – and optimize – nursing care for patients with arthritis.

The recommendations, presented May 25 at the annual European Congress of Rheumatology by Yvonne van Eijk-Hustings, were developed by the EULAR Nursing Task Force, which consists of nurses, rheumatologists, an occupational therapist, a physiotherapist, a psychologist, an epidemiologist, and patient representatives from 14 European countries.

    Yvonne van Eijk-Hustings

"The role of the nurse in rheumatology is undergoing great changes," said Ms. van Eijk-Hustings. "Nurses should participate in comprehensive disease management to control disease activity, reduce symptoms, and improve outcomes."

The panel conducted a systematic literature search of the Medline, Embase, Cochrane library, CINAHL, and PscychINFO databases, plus abstracts from the last three American College of Rheumatology and EULAR conferences. They ultimately consulted a total of 54 studies.

In general, said Ms. van Eijk-Hustings, the researchers’ findings support the conclusion that nurses play an important part of a necessarily multidisciplinary team of caregivers that – in addition to rheumatologists – also includes physical therapists, occupational therapists, and psychologists.

"Being involved in the disease process provides nurses with the opportunity to recognize and point out problems in an early stage, which ensures timely interventions and timely referral to other members of the multidisciplinary team," said Ms. van Eijk-Hustings of the department of integrated care at Maastricht (the Netherlands) University Medical Centre.

However, "our project showed that the contribution of nurses to multidisciplinary care is not clearly stated and that competencies and skills of nurses are often not optimally used," according to Ms. Van Eijk-Hustings.

Ultimately, the panel developed 10 recommendations, 7 of which deal with nurses’ ideal contribution to the areas of patient education, satisfaction with care, access to care, psychosocial support, disease management, self-management, and efficiency of care.

Three additional recommendations outline the need for professional support for nurses, including increasing the availability of guidelines or nursing protocols, increasing access to education, and encouraging nurses to undertake extended roles in rheumatology.

"In general, it is of importance that patients have access to rheumatology nurses for various reasons and that rheumatology nurses have access to appropriate training and education in order to maintain and improve their knowledge and skills," said Ms. Van Eijk-Hustings, a registered nurse and doctoral candidate whose own current research deals with the evolving roles of nurses in changing health care systems in different countries. 

"This includes advanced, more autonomous roles for nurses, as well as substitution of tasks in the management of chronic disorders without loss of typical nursing skills," she added.

The task force also highlighted ten topics for future research, including the need for high-quality quantitative and qualitative studies with clear descriptions of nursing roles and interventions.

"One important area to mention is the contribution of the nurse in improving patient-preferred outcomes," added Ms. Van Eijk-Hustings.

The researchers cautioned that although the recommendations are likely to be applicable to the role of nurses in other rheumatic diseases, "in the present project, we focused on rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and most evidence was found with regard to rheumatoid arthritis."

EULAR support is needed for further dissemination and evaluation of the recommendations, she added.

The researchers reported having no disclosures to make in relation to this study.

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The role of the nurse in rheumatology varies widely among countries, in large part because of differences in legal regulations, as well as nurses’ educational background and funding issues related to overall health care provision.

However, a new set of recommendations aims to standardize – and optimize – nursing care for patients with arthritis.

The recommendations, presented May 25 at the annual European Congress of Rheumatology by Yvonne van Eijk-Hustings, were developed by the EULAR Nursing Task Force, which consists of nurses, rheumatologists, an occupational therapist, a physiotherapist, a psychologist, an epidemiologist, and patient representatives from 14 European countries.

    Yvonne van Eijk-Hustings

"The role of the nurse in rheumatology is undergoing great changes," said Ms. van Eijk-Hustings. "Nurses should participate in comprehensive disease management to control disease activity, reduce symptoms, and improve outcomes."

The panel conducted a systematic literature search of the Medline, Embase, Cochrane library, CINAHL, and PscychINFO databases, plus abstracts from the last three American College of Rheumatology and EULAR conferences. They ultimately consulted a total of 54 studies.

In general, said Ms. van Eijk-Hustings, the researchers’ findings support the conclusion that nurses play an important part of a necessarily multidisciplinary team of caregivers that – in addition to rheumatologists – also includes physical therapists, occupational therapists, and psychologists.

"Being involved in the disease process provides nurses with the opportunity to recognize and point out problems in an early stage, which ensures timely interventions and timely referral to other members of the multidisciplinary team," said Ms. van Eijk-Hustings of the department of integrated care at Maastricht (the Netherlands) University Medical Centre.

However, "our project showed that the contribution of nurses to multidisciplinary care is not clearly stated and that competencies and skills of nurses are often not optimally used," according to Ms. Van Eijk-Hustings.

Ultimately, the panel developed 10 recommendations, 7 of which deal with nurses’ ideal contribution to the areas of patient education, satisfaction with care, access to care, psychosocial support, disease management, self-management, and efficiency of care.

Three additional recommendations outline the need for professional support for nurses, including increasing the availability of guidelines or nursing protocols, increasing access to education, and encouraging nurses to undertake extended roles in rheumatology.

"In general, it is of importance that patients have access to rheumatology nurses for various reasons and that rheumatology nurses have access to appropriate training and education in order to maintain and improve their knowledge and skills," said Ms. Van Eijk-Hustings, a registered nurse and doctoral candidate whose own current research deals with the evolving roles of nurses in changing health care systems in different countries. 

"This includes advanced, more autonomous roles for nurses, as well as substitution of tasks in the management of chronic disorders without loss of typical nursing skills," she added.

The task force also highlighted ten topics for future research, including the need for high-quality quantitative and qualitative studies with clear descriptions of nursing roles and interventions.

"One important area to mention is the contribution of the nurse in improving patient-preferred outcomes," added Ms. Van Eijk-Hustings.

The researchers cautioned that although the recommendations are likely to be applicable to the role of nurses in other rheumatic diseases, "in the present project, we focused on rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and most evidence was found with regard to rheumatoid arthritis."

EULAR support is needed for further dissemination and evaluation of the recommendations, she added.

The researchers reported having no disclosures to make in relation to this study.

The role of the nurse in rheumatology varies widely among countries, in large part because of differences in legal regulations, as well as nurses’ educational background and funding issues related to overall health care provision.

However, a new set of recommendations aims to standardize – and optimize – nursing care for patients with arthritis.

The recommendations, presented May 25 at the annual European Congress of Rheumatology by Yvonne van Eijk-Hustings, were developed by the EULAR Nursing Task Force, which consists of nurses, rheumatologists, an occupational therapist, a physiotherapist, a psychologist, an epidemiologist, and patient representatives from 14 European countries.

    Yvonne van Eijk-Hustings

"The role of the nurse in rheumatology is undergoing great changes," said Ms. van Eijk-Hustings. "Nurses should participate in comprehensive disease management to control disease activity, reduce symptoms, and improve outcomes."

The panel conducted a systematic literature search of the Medline, Embase, Cochrane library, CINAHL, and PscychINFO databases, plus abstracts from the last three American College of Rheumatology and EULAR conferences. They ultimately consulted a total of 54 studies.

In general, said Ms. van Eijk-Hustings, the researchers’ findings support the conclusion that nurses play an important part of a necessarily multidisciplinary team of caregivers that – in addition to rheumatologists – also includes physical therapists, occupational therapists, and psychologists.

"Being involved in the disease process provides nurses with the opportunity to recognize and point out problems in an early stage, which ensures timely interventions and timely referral to other members of the multidisciplinary team," said Ms. van Eijk-Hustings of the department of integrated care at Maastricht (the Netherlands) University Medical Centre.

However, "our project showed that the contribution of nurses to multidisciplinary care is not clearly stated and that competencies and skills of nurses are often not optimally used," according to Ms. Van Eijk-Hustings.

Ultimately, the panel developed 10 recommendations, 7 of which deal with nurses’ ideal contribution to the areas of patient education, satisfaction with care, access to care, psychosocial support, disease management, self-management, and efficiency of care.

Three additional recommendations outline the need for professional support for nurses, including increasing the availability of guidelines or nursing protocols, increasing access to education, and encouraging nurses to undertake extended roles in rheumatology.

"In general, it is of importance that patients have access to rheumatology nurses for various reasons and that rheumatology nurses have access to appropriate training and education in order to maintain and improve their knowledge and skills," said Ms. Van Eijk-Hustings, a registered nurse and doctoral candidate whose own current research deals with the evolving roles of nurses in changing health care systems in different countries. 

"This includes advanced, more autonomous roles for nurses, as well as substitution of tasks in the management of chronic disorders without loss of typical nursing skills," she added.

The task force also highlighted ten topics for future research, including the need for high-quality quantitative and qualitative studies with clear descriptions of nursing roles and interventions.

"One important area to mention is the contribution of the nurse in improving patient-preferred outcomes," added Ms. Van Eijk-Hustings.

The researchers cautioned that although the recommendations are likely to be applicable to the role of nurses in other rheumatic diseases, "in the present project, we focused on rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and most evidence was found with regard to rheumatoid arthritis."

EULAR support is needed for further dissemination and evaluation of the recommendations, she added.

The researchers reported having no disclosures to make in relation to this study.

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New Recommendations Outline Nurses' Role in Arthritis Care

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The role of the nurse in rheumatology varies widely among countries, in large part because of differences in legal regulations, as well as nurses’ educational background and funding issues related to overall health care provision.

However, a new set of recommendations aims to standardize – and optimize – nursing care for patients with arthritis.

The recommendations, presented May 25 at the annual European Congress of Rheumatology by Yvonne van Eijk-Hustings, were developed by the EULAR Nursing Task Force, which consists of nurses, rheumatologists, an occupational therapist, a physiotherapist, a psychologist, an epidemiologist, and patient representatives from 14 European countries.

    Yvonne van Eijk-Hustings

"The role of the nurse in rheumatology is undergoing great changes," said Ms. van Eijk-Hustings. "Nurses should participate in comprehensive disease management to control disease activity, reduce symptoms, and improve outcomes."

The panel conducted a systematic literature search of the Medline, Embase, Cochrane library, CINAHL, and PscychINFO databases, plus abstracts from the last three American College of Rheumatology and EULAR conferences. They ultimately consulted a total of 54 studies.

In general, said Ms. van Eijk-Hustings, the researchers’ findings support the conclusion that nurses play an important part of a necessarily multidisciplinary team of caregivers that – in addition to rheumatologists – also includes physical therapists, occupational therapists, and psychologists.

"Being involved in the disease process provides nurses with the opportunity to recognize and point out problems in an early stage, which ensures timely interventions and timely referral to other members of the multidisciplinary team," said Ms. van Eijk-Hustings of the department of integrated care at Maastricht (the Netherlands) University Medical Centre.

However, "our project showed that the contribution of nurses to multidisciplinary care is not clearly stated and that competencies and skills of nurses are often not optimally used," according to Ms. Van Eijk-Hustings.

Ultimately, the panel developed 10 recommendations, 7 of which deal with nurses’ ideal contribution to the areas of patient education, satisfaction with care, access to care, psychosocial support, disease management, self-management, and efficiency of care.

Three additional recommendations outline the need for professional support for nurses, including increasing the availability of guidelines or nursing protocols, increasing access to education, and encouraging nurses to undertake extended roles in rheumatology.

"In general, it is of importance that patients have access to rheumatology nurses for various reasons and that rheumatology nurses have access to appropriate training and education in order to maintain and improve their knowledge and skills," said Ms. Van Eijk-Hustings, a registered nurse and doctoral candidate whose own current research deals with the evolving roles of nurses in changing health care systems in different countries. 

"This includes advanced, more autonomous roles for nurses, as well as substitution of tasks in the management of chronic disorders without loss of typical nursing skills," she added.

The task force also highlighted ten topics for future research, including the need for high-quality quantitative and qualitative studies with clear descriptions of nursing roles and interventions.

"One important area to mention is the contribution of the nurse in improving patient-preferred outcomes," added Ms. Van Eijk-Hustings.

The researchers cautioned that although the recommendations are likely to be applicable to the role of nurses in other rheumatic diseases, "in the present project, we focused on rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and most evidence was found with regard to rheumatoid arthritis."

EULAR support is needed for further dissemination and evaluation of the recommendations, she added.

The researchers reported having no disclosures to make in relation to this study.

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The role of the nurse in rheumatology varies widely among countries, in large part because of differences in legal regulations, as well as nurses’ educational background and funding issues related to overall health care provision.

However, a new set of recommendations aims to standardize – and optimize – nursing care for patients with arthritis.

The recommendations, presented May 25 at the annual European Congress of Rheumatology by Yvonne van Eijk-Hustings, were developed by the EULAR Nursing Task Force, which consists of nurses, rheumatologists, an occupational therapist, a physiotherapist, a psychologist, an epidemiologist, and patient representatives from 14 European countries.

    Yvonne van Eijk-Hustings

"The role of the nurse in rheumatology is undergoing great changes," said Ms. van Eijk-Hustings. "Nurses should participate in comprehensive disease management to control disease activity, reduce symptoms, and improve outcomes."

The panel conducted a systematic literature search of the Medline, Embase, Cochrane library, CINAHL, and PscychINFO databases, plus abstracts from the last three American College of Rheumatology and EULAR conferences. They ultimately consulted a total of 54 studies.

In general, said Ms. van Eijk-Hustings, the researchers’ findings support the conclusion that nurses play an important part of a necessarily multidisciplinary team of caregivers that – in addition to rheumatologists – also includes physical therapists, occupational therapists, and psychologists.

"Being involved in the disease process provides nurses with the opportunity to recognize and point out problems in an early stage, which ensures timely interventions and timely referral to other members of the multidisciplinary team," said Ms. van Eijk-Hustings of the department of integrated care at Maastricht (the Netherlands) University Medical Centre.

However, "our project showed that the contribution of nurses to multidisciplinary care is not clearly stated and that competencies and skills of nurses are often not optimally used," according to Ms. Van Eijk-Hustings.

Ultimately, the panel developed 10 recommendations, 7 of which deal with nurses’ ideal contribution to the areas of patient education, satisfaction with care, access to care, psychosocial support, disease management, self-management, and efficiency of care.

Three additional recommendations outline the need for professional support for nurses, including increasing the availability of guidelines or nursing protocols, increasing access to education, and encouraging nurses to undertake extended roles in rheumatology.

"In general, it is of importance that patients have access to rheumatology nurses for various reasons and that rheumatology nurses have access to appropriate training and education in order to maintain and improve their knowledge and skills," said Ms. Van Eijk-Hustings, a registered nurse and doctoral candidate whose own current research deals with the evolving roles of nurses in changing health care systems in different countries. 

"This includes advanced, more autonomous roles for nurses, as well as substitution of tasks in the management of chronic disorders without loss of typical nursing skills," she added.

The task force also highlighted ten topics for future research, including the need for high-quality quantitative and qualitative studies with clear descriptions of nursing roles and interventions.

"One important area to mention is the contribution of the nurse in improving patient-preferred outcomes," added Ms. Van Eijk-Hustings.

The researchers cautioned that although the recommendations are likely to be applicable to the role of nurses in other rheumatic diseases, "in the present project, we focused on rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and most evidence was found with regard to rheumatoid arthritis."

EULAR support is needed for further dissemination and evaluation of the recommendations, she added.

The researchers reported having no disclosures to make in relation to this study.

The role of the nurse in rheumatology varies widely among countries, in large part because of differences in legal regulations, as well as nurses’ educational background and funding issues related to overall health care provision.

However, a new set of recommendations aims to standardize – and optimize – nursing care for patients with arthritis.

The recommendations, presented May 25 at the annual European Congress of Rheumatology by Yvonne van Eijk-Hustings, were developed by the EULAR Nursing Task Force, which consists of nurses, rheumatologists, an occupational therapist, a physiotherapist, a psychologist, an epidemiologist, and patient representatives from 14 European countries.

    Yvonne van Eijk-Hustings

"The role of the nurse in rheumatology is undergoing great changes," said Ms. van Eijk-Hustings. "Nurses should participate in comprehensive disease management to control disease activity, reduce symptoms, and improve outcomes."

The panel conducted a systematic literature search of the Medline, Embase, Cochrane library, CINAHL, and PscychINFO databases, plus abstracts from the last three American College of Rheumatology and EULAR conferences. They ultimately consulted a total of 54 studies.

In general, said Ms. van Eijk-Hustings, the researchers’ findings support the conclusion that nurses play an important part of a necessarily multidisciplinary team of caregivers that – in addition to rheumatologists – also includes physical therapists, occupational therapists, and psychologists.

"Being involved in the disease process provides nurses with the opportunity to recognize and point out problems in an early stage, which ensures timely interventions and timely referral to other members of the multidisciplinary team," said Ms. van Eijk-Hustings of the department of integrated care at Maastricht (the Netherlands) University Medical Centre.

However, "our project showed that the contribution of nurses to multidisciplinary care is not clearly stated and that competencies and skills of nurses are often not optimally used," according to Ms. Van Eijk-Hustings.

Ultimately, the panel developed 10 recommendations, 7 of which deal with nurses’ ideal contribution to the areas of patient education, satisfaction with care, access to care, psychosocial support, disease management, self-management, and efficiency of care.

Three additional recommendations outline the need for professional support for nurses, including increasing the availability of guidelines or nursing protocols, increasing access to education, and encouraging nurses to undertake extended roles in rheumatology.

"In general, it is of importance that patients have access to rheumatology nurses for various reasons and that rheumatology nurses have access to appropriate training and education in order to maintain and improve their knowledge and skills," said Ms. Van Eijk-Hustings, a registered nurse and doctoral candidate whose own current research deals with the evolving roles of nurses in changing health care systems in different countries. 

"This includes advanced, more autonomous roles for nurses, as well as substitution of tasks in the management of chronic disorders without loss of typical nursing skills," she added.

The task force also highlighted ten topics for future research, including the need for high-quality quantitative and qualitative studies with clear descriptions of nursing roles and interventions.

"One important area to mention is the contribution of the nurse in improving patient-preferred outcomes," added Ms. Van Eijk-Hustings.

The researchers cautioned that although the recommendations are likely to be applicable to the role of nurses in other rheumatic diseases, "in the present project, we focused on rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, and most evidence was found with regard to rheumatoid arthritis."

EULAR support is needed for further dissemination and evaluation of the recommendations, she added.

The researchers reported having no disclosures to make in relation to this study.

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Cartilage Loss More Disabling Than Erosion in RA

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Cartilage Loss More Disabling Than Erosion in RA

When it comes to disability in rheumatoid arthritis, it is cartilage loss – not bone damage – that seems to have the greater effect.

Accordingly, therapeutic interventions that aim to reduce disability should focus on cartilage preservation, "since even relatively little cartilage degradation can lead to significant impairment of physical functioning," wrote Dr. Daniel Aletaha of the Medical University of Vienna and his colleagues in the May issue of Annals of the Rheumatic Diseases.

The authors looked at data from a pool of 4,602 participants in various clinical trials of adalimumab, methotrexate, infliximab, and leflunomide. "To separate the reversible, RA activity–related component of disability from the irreversible component, we identified patients who achieved clinical remission during the trials [that is, a state of absence of significant RA activity and thus the absence of a reversible disability component]," Dr. Aletaha and his colleagues wrote (Ann. Rheum. Dis. 2011;70:733-9).

Remission was defined as an SDAI (Simplified Disease Activity Index) score of 3.3 or less.

In all, 748 patients were included in the current analysis. Patient data were assessed at the first visit in which a patient was in remission, and that visit’s corresponding HAQ-DI (Health Assessment Questionnaire–Disability Index) score was used as "the best estimate of the patient’s irreversible functional disability" for the current study, they wrote.

The HAQ-DI scale has a 0-3 range, with 0 indicating no difficulty in the activities of daily living, and 3 indicating complete disability.

Patients were divided into tertiles according to the degree of both joint space narrowing (JSN), which is a function of cartilage loss, and bone erosion (ERO). As expected, in univariate analysis, the mean scores on the HAQ-DI increased – indicating greater disability – as JSN/ERO tertiles increased (0.21, 0.24, and 0.35, respectively, for the first, second, and third tertiles; P less than .0001).

"Likewise and even to a numerically greater extent, with increasing tertiles by JSN, residual (irreversible) HAQ-DI scores increased," wrote the authors, with a mean of 0.18, 0.24, and 0.38 for the first, second, and third tertiles, respectively (P less than .0001).

To assess the independent disability contribution of erosion vs. narrowing, the authors then looked at the effects of higher erosion tertiles within each of the JSN tertiles. In other words, within each tertile of JSN, patients were further stratified into tertiles of ERO, and the HAQ-DI scores were compared.

"In the first and second tertiles formed according to JSN, higher degrees of erosive changes did not contribute at all to irreversible disability," such that HAQ-DI scores did not differ significantly between ERO tertiles (P = .99 and .77, respectively), they said.

Although patients in the third quartiles of both JSN and ERO did have significantly greater HAQ-DI scores than did patients with less-severe bone erosion (0.417; P = .07), this was an expected finding, wrote the authors, as this group includes patients with severe joint damage.

However, when patients were first divided into ERO tertiles, and then further subdivided according to JSN severity within each tertile, the authors did find a significant effect on disability according to the HAQ-DI.

Indeed, within all three ERO strata, increasing JSN significantly corresponded with increasing HAQ-DI scores (P less than .05, P = .19, and P less than .001 for the first, second, and third ERO tertiles, respectively).

Despite the fact that bony erosion is considered "prototypic for RA," whereas joint space narrowing (which occurs in other disorders) is considered less characteristic of the disease, "in the present study we have been able to show that the clinical impact of joint destruction cartilage loss seems to be of much higher relevance than damage to the bone," Dr. Aletaha and his coauthors wrote.

"The data presented here provide sufficient evidence for developing, and further testing of, the hypothesis that cartilage damage, rather than bone destruction, may constitute the pivotal cause of physical functional impairment in RA," they concluded.

Data were provided by Abbott, Amgen, Centocor, Sanofi-Aventis and Wyeth (later acquired by Pfizer). None of the authors disclosed any personal competing interests in relation to this study.

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When it comes to disability in rheumatoid arthritis, it is cartilage loss – not bone damage – that seems to have the greater effect.

Accordingly, therapeutic interventions that aim to reduce disability should focus on cartilage preservation, "since even relatively little cartilage degradation can lead to significant impairment of physical functioning," wrote Dr. Daniel Aletaha of the Medical University of Vienna and his colleagues in the May issue of Annals of the Rheumatic Diseases.

The authors looked at data from a pool of 4,602 participants in various clinical trials of adalimumab, methotrexate, infliximab, and leflunomide. "To separate the reversible, RA activity–related component of disability from the irreversible component, we identified patients who achieved clinical remission during the trials [that is, a state of absence of significant RA activity and thus the absence of a reversible disability component]," Dr. Aletaha and his colleagues wrote (Ann. Rheum. Dis. 2011;70:733-9).

Remission was defined as an SDAI (Simplified Disease Activity Index) score of 3.3 or less.

In all, 748 patients were included in the current analysis. Patient data were assessed at the first visit in which a patient was in remission, and that visit’s corresponding HAQ-DI (Health Assessment Questionnaire–Disability Index) score was used as "the best estimate of the patient’s irreversible functional disability" for the current study, they wrote.

The HAQ-DI scale has a 0-3 range, with 0 indicating no difficulty in the activities of daily living, and 3 indicating complete disability.

Patients were divided into tertiles according to the degree of both joint space narrowing (JSN), which is a function of cartilage loss, and bone erosion (ERO). As expected, in univariate analysis, the mean scores on the HAQ-DI increased – indicating greater disability – as JSN/ERO tertiles increased (0.21, 0.24, and 0.35, respectively, for the first, second, and third tertiles; P less than .0001).

"Likewise and even to a numerically greater extent, with increasing tertiles by JSN, residual (irreversible) HAQ-DI scores increased," wrote the authors, with a mean of 0.18, 0.24, and 0.38 for the first, second, and third tertiles, respectively (P less than .0001).

To assess the independent disability contribution of erosion vs. narrowing, the authors then looked at the effects of higher erosion tertiles within each of the JSN tertiles. In other words, within each tertile of JSN, patients were further stratified into tertiles of ERO, and the HAQ-DI scores were compared.

"In the first and second tertiles formed according to JSN, higher degrees of erosive changes did not contribute at all to irreversible disability," such that HAQ-DI scores did not differ significantly between ERO tertiles (P = .99 and .77, respectively), they said.

Although patients in the third quartiles of both JSN and ERO did have significantly greater HAQ-DI scores than did patients with less-severe bone erosion (0.417; P = .07), this was an expected finding, wrote the authors, as this group includes patients with severe joint damage.

However, when patients were first divided into ERO tertiles, and then further subdivided according to JSN severity within each tertile, the authors did find a significant effect on disability according to the HAQ-DI.

Indeed, within all three ERO strata, increasing JSN significantly corresponded with increasing HAQ-DI scores (P less than .05, P = .19, and P less than .001 for the first, second, and third ERO tertiles, respectively).

Despite the fact that bony erosion is considered "prototypic for RA," whereas joint space narrowing (which occurs in other disorders) is considered less characteristic of the disease, "in the present study we have been able to show that the clinical impact of joint destruction cartilage loss seems to be of much higher relevance than damage to the bone," Dr. Aletaha and his coauthors wrote.

"The data presented here provide sufficient evidence for developing, and further testing of, the hypothesis that cartilage damage, rather than bone destruction, may constitute the pivotal cause of physical functional impairment in RA," they concluded.

Data were provided by Abbott, Amgen, Centocor, Sanofi-Aventis and Wyeth (later acquired by Pfizer). None of the authors disclosed any personal competing interests in relation to this study.

When it comes to disability in rheumatoid arthritis, it is cartilage loss – not bone damage – that seems to have the greater effect.

Accordingly, therapeutic interventions that aim to reduce disability should focus on cartilage preservation, "since even relatively little cartilage degradation can lead to significant impairment of physical functioning," wrote Dr. Daniel Aletaha of the Medical University of Vienna and his colleagues in the May issue of Annals of the Rheumatic Diseases.

The authors looked at data from a pool of 4,602 participants in various clinical trials of adalimumab, methotrexate, infliximab, and leflunomide. "To separate the reversible, RA activity–related component of disability from the irreversible component, we identified patients who achieved clinical remission during the trials [that is, a state of absence of significant RA activity and thus the absence of a reversible disability component]," Dr. Aletaha and his colleagues wrote (Ann. Rheum. Dis. 2011;70:733-9).

Remission was defined as an SDAI (Simplified Disease Activity Index) score of 3.3 or less.

In all, 748 patients were included in the current analysis. Patient data were assessed at the first visit in which a patient was in remission, and that visit’s corresponding HAQ-DI (Health Assessment Questionnaire–Disability Index) score was used as "the best estimate of the patient’s irreversible functional disability" for the current study, they wrote.

The HAQ-DI scale has a 0-3 range, with 0 indicating no difficulty in the activities of daily living, and 3 indicating complete disability.

Patients were divided into tertiles according to the degree of both joint space narrowing (JSN), which is a function of cartilage loss, and bone erosion (ERO). As expected, in univariate analysis, the mean scores on the HAQ-DI increased – indicating greater disability – as JSN/ERO tertiles increased (0.21, 0.24, and 0.35, respectively, for the first, second, and third tertiles; P less than .0001).

"Likewise and even to a numerically greater extent, with increasing tertiles by JSN, residual (irreversible) HAQ-DI scores increased," wrote the authors, with a mean of 0.18, 0.24, and 0.38 for the first, second, and third tertiles, respectively (P less than .0001).

To assess the independent disability contribution of erosion vs. narrowing, the authors then looked at the effects of higher erosion tertiles within each of the JSN tertiles. In other words, within each tertile of JSN, patients were further stratified into tertiles of ERO, and the HAQ-DI scores were compared.

"In the first and second tertiles formed according to JSN, higher degrees of erosive changes did not contribute at all to irreversible disability," such that HAQ-DI scores did not differ significantly between ERO tertiles (P = .99 and .77, respectively), they said.

Although patients in the third quartiles of both JSN and ERO did have significantly greater HAQ-DI scores than did patients with less-severe bone erosion (0.417; P = .07), this was an expected finding, wrote the authors, as this group includes patients with severe joint damage.

However, when patients were first divided into ERO tertiles, and then further subdivided according to JSN severity within each tertile, the authors did find a significant effect on disability according to the HAQ-DI.

Indeed, within all three ERO strata, increasing JSN significantly corresponded with increasing HAQ-DI scores (P less than .05, P = .19, and P less than .001 for the first, second, and third ERO tertiles, respectively).

Despite the fact that bony erosion is considered "prototypic for RA," whereas joint space narrowing (which occurs in other disorders) is considered less characteristic of the disease, "in the present study we have been able to show that the clinical impact of joint destruction cartilage loss seems to be of much higher relevance than damage to the bone," Dr. Aletaha and his coauthors wrote.

"The data presented here provide sufficient evidence for developing, and further testing of, the hypothesis that cartilage damage, rather than bone destruction, may constitute the pivotal cause of physical functional impairment in RA," they concluded.

Data were provided by Abbott, Amgen, Centocor, Sanofi-Aventis and Wyeth (later acquired by Pfizer). None of the authors disclosed any personal competing interests in relation to this study.

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Major Finding: Joint space narrowing significantly corresponded with increasing disability in patients with rheumatoid arthritis.

Data Source: Pooled data from several clinical trials of patients in remission from rheumatoid arthritis.

Disclosures: Data were provided by Abbott, Amgen, Centocor, Sanofi-Aventis, and Wyeth (later acquired by Pfizer). None of the authors disclosed financial conflicts of interest in relation to this study.

Cartilage Loss More Disabling Than Erosion in RA

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Cartilage Loss More Disabling Than Erosion in RA

When it comes to disability in rheumatoid arthritis, it is cartilage loss – not bone damage – that seems to have the greater effect.

Accordingly, therapeutic interventions that aim to reduce disability should focus on cartilage preservation, "since even relatively little cartilage degradation can lead to significant impairment of physical functioning," wrote Dr. Daniel Aletaha of the Medical University of Vienna and his colleagues in the May issue of Annals of the Rheumatic Diseases.

The authors looked at data from a pool of 4,602 participants in various clinical trials of adalimumab, methotrexate, infliximab, and leflunomide. "To separate the reversible, RA activity–related component of disability from the irreversible component, we identified patients who achieved clinical remission during the trials [that is, a state of absence of significant RA activity and thus the absence of a reversible disability component]," Dr. Aletaha and his colleagues wrote (Ann. Rheum. Dis. 2011;70:733-9).

Remission was defined as an SDAI (Simplified Disease Activity Index) score of 3.3 or less.

In all, 748 patients were included in the current analysis. Patient data were assessed at the first visit in which a patient was in remission, and that visit’s corresponding HAQ-DI (Health Assessment Questionnaire–Disability Index) score was used as "the best estimate of the patient’s irreversible functional disability" for the current study, they wrote.

The HAQ-DI scale has a 0-3 range, with 0 indicating no difficulty in the activities of daily living, and 3 indicating complete disability.

Patients were divided into tertiles according to the degree of both joint space narrowing (JSN), which is a function of cartilage loss, and bone erosion (ERO). As expected, in univariate analysis, the mean scores on the HAQ-DI increased – indicating greater disability – as JSN/ERO tertiles increased (0.21, 0.24, and 0.35, respectively, for the first, second, and third tertiles; P less than .0001).

"Likewise and even to a numerically greater extent, with increasing tertiles by JSN, residual (irreversible) HAQ-DI scores increased," wrote the authors, with a mean of 0.18, 0.24, and 0.38 for the first, second, and third tertiles, respectively (P less than .0001).

To assess the independent disability contribution of erosion vs. narrowing, the authors then looked at the effects of higher erosion tertiles within each of the JSN tertiles. In other words, within each tertile of JSN, patients were further stratified into tertiles of ERO, and the HAQ-DI scores were compared.

"In the first and second tertiles formed according to JSN, higher degrees of erosive changes did not contribute at all to irreversible disability," such that HAQ-DI scores did not differ significantly between ERO tertiles (P = .99 and .77, respectively), they said.

Although patients in the third quartiles of both JSN and ERO did have significantly greater HAQ-DI scores than did patients with less-severe bone erosion (0.417; P = .07), this was an expected finding, wrote the authors, as this group includes patients with severe joint damage.

However, when patients were first divided into ERO tertiles, and then further subdivided according to JSN severity within each tertile, the authors did find a significant effect on disability according to the HAQ-DI.

Indeed, within all three ERO strata, increasing JSN significantly corresponded with increasing HAQ-DI scores (P less than .05, P = .19, and P less than .001 for the first, second, and third ERO tertiles, respectively).

Despite the fact that bony erosion is considered "prototypic for RA," whereas joint space narrowing (which occurs in other disorders) is considered less characteristic of the disease, "in the present study we have been able to show that the clinical impact of joint destruction cartilage loss seems to be of much higher relevance than damage to the bone," Dr. Aletaha and his coauthors wrote.

"The data presented here provide sufficient evidence for developing, and further testing of, the hypothesis that cartilage damage, rather than bone destruction, may constitute the pivotal cause of physical functional impairment in RA," they concluded.

Data were provided by Abbott, Amgen, Centocor, Sanofi-Aventis and Wyeth (later acquired by Pfizer). None of the authors disclosed any personal competing interests in relation to this study.

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When it comes to disability in rheumatoid arthritis, it is cartilage loss – not bone damage – that seems to have the greater effect.

Accordingly, therapeutic interventions that aim to reduce disability should focus on cartilage preservation, "since even relatively little cartilage degradation can lead to significant impairment of physical functioning," wrote Dr. Daniel Aletaha of the Medical University of Vienna and his colleagues in the May issue of Annals of the Rheumatic Diseases.

The authors looked at data from a pool of 4,602 participants in various clinical trials of adalimumab, methotrexate, infliximab, and leflunomide. "To separate the reversible, RA activity–related component of disability from the irreversible component, we identified patients who achieved clinical remission during the trials [that is, a state of absence of significant RA activity and thus the absence of a reversible disability component]," Dr. Aletaha and his colleagues wrote (Ann. Rheum. Dis. 2011;70:733-9).

Remission was defined as an SDAI (Simplified Disease Activity Index) score of 3.3 or less.

In all, 748 patients were included in the current analysis. Patient data were assessed at the first visit in which a patient was in remission, and that visit’s corresponding HAQ-DI (Health Assessment Questionnaire–Disability Index) score was used as "the best estimate of the patient’s irreversible functional disability" for the current study, they wrote.

The HAQ-DI scale has a 0-3 range, with 0 indicating no difficulty in the activities of daily living, and 3 indicating complete disability.

Patients were divided into tertiles according to the degree of both joint space narrowing (JSN), which is a function of cartilage loss, and bone erosion (ERO). As expected, in univariate analysis, the mean scores on the HAQ-DI increased – indicating greater disability – as JSN/ERO tertiles increased (0.21, 0.24, and 0.35, respectively, for the first, second, and third tertiles; P less than .0001).

"Likewise and even to a numerically greater extent, with increasing tertiles by JSN, residual (irreversible) HAQ-DI scores increased," wrote the authors, with a mean of 0.18, 0.24, and 0.38 for the first, second, and third tertiles, respectively (P less than .0001).

To assess the independent disability contribution of erosion vs. narrowing, the authors then looked at the effects of higher erosion tertiles within each of the JSN tertiles. In other words, within each tertile of JSN, patients were further stratified into tertiles of ERO, and the HAQ-DI scores were compared.

"In the first and second tertiles formed according to JSN, higher degrees of erosive changes did not contribute at all to irreversible disability," such that HAQ-DI scores did not differ significantly between ERO tertiles (P = .99 and .77, respectively), they said.

Although patients in the third quartiles of both JSN and ERO did have significantly greater HAQ-DI scores than did patients with less-severe bone erosion (0.417; P = .07), this was an expected finding, wrote the authors, as this group includes patients with severe joint damage.

However, when patients were first divided into ERO tertiles, and then further subdivided according to JSN severity within each tertile, the authors did find a significant effect on disability according to the HAQ-DI.

Indeed, within all three ERO strata, increasing JSN significantly corresponded with increasing HAQ-DI scores (P less than .05, P = .19, and P less than .001 for the first, second, and third ERO tertiles, respectively).

Despite the fact that bony erosion is considered "prototypic for RA," whereas joint space narrowing (which occurs in other disorders) is considered less characteristic of the disease, "in the present study we have been able to show that the clinical impact of joint destruction cartilage loss seems to be of much higher relevance than damage to the bone," Dr. Aletaha and his coauthors wrote.

"The data presented here provide sufficient evidence for developing, and further testing of, the hypothesis that cartilage damage, rather than bone destruction, may constitute the pivotal cause of physical functional impairment in RA," they concluded.

Data were provided by Abbott, Amgen, Centocor, Sanofi-Aventis and Wyeth (later acquired by Pfizer). None of the authors disclosed any personal competing interests in relation to this study.

When it comes to disability in rheumatoid arthritis, it is cartilage loss – not bone damage – that seems to have the greater effect.

Accordingly, therapeutic interventions that aim to reduce disability should focus on cartilage preservation, "since even relatively little cartilage degradation can lead to significant impairment of physical functioning," wrote Dr. Daniel Aletaha of the Medical University of Vienna and his colleagues in the May issue of Annals of the Rheumatic Diseases.

The authors looked at data from a pool of 4,602 participants in various clinical trials of adalimumab, methotrexate, infliximab, and leflunomide. "To separate the reversible, RA activity–related component of disability from the irreversible component, we identified patients who achieved clinical remission during the trials [that is, a state of absence of significant RA activity and thus the absence of a reversible disability component]," Dr. Aletaha and his colleagues wrote (Ann. Rheum. Dis. 2011;70:733-9).

Remission was defined as an SDAI (Simplified Disease Activity Index) score of 3.3 or less.

In all, 748 patients were included in the current analysis. Patient data were assessed at the first visit in which a patient was in remission, and that visit’s corresponding HAQ-DI (Health Assessment Questionnaire–Disability Index) score was used as "the best estimate of the patient’s irreversible functional disability" for the current study, they wrote.

The HAQ-DI scale has a 0-3 range, with 0 indicating no difficulty in the activities of daily living, and 3 indicating complete disability.

Patients were divided into tertiles according to the degree of both joint space narrowing (JSN), which is a function of cartilage loss, and bone erosion (ERO). As expected, in univariate analysis, the mean scores on the HAQ-DI increased – indicating greater disability – as JSN/ERO tertiles increased (0.21, 0.24, and 0.35, respectively, for the first, second, and third tertiles; P less than .0001).

"Likewise and even to a numerically greater extent, with increasing tertiles by JSN, residual (irreversible) HAQ-DI scores increased," wrote the authors, with a mean of 0.18, 0.24, and 0.38 for the first, second, and third tertiles, respectively (P less than .0001).

To assess the independent disability contribution of erosion vs. narrowing, the authors then looked at the effects of higher erosion tertiles within each of the JSN tertiles. In other words, within each tertile of JSN, patients were further stratified into tertiles of ERO, and the HAQ-DI scores were compared.

"In the first and second tertiles formed according to JSN, higher degrees of erosive changes did not contribute at all to irreversible disability," such that HAQ-DI scores did not differ significantly between ERO tertiles (P = .99 and .77, respectively), they said.

Although patients in the third quartiles of both JSN and ERO did have significantly greater HAQ-DI scores than did patients with less-severe bone erosion (0.417; P = .07), this was an expected finding, wrote the authors, as this group includes patients with severe joint damage.

However, when patients were first divided into ERO tertiles, and then further subdivided according to JSN severity within each tertile, the authors did find a significant effect on disability according to the HAQ-DI.

Indeed, within all three ERO strata, increasing JSN significantly corresponded with increasing HAQ-DI scores (P less than .05, P = .19, and P less than .001 for the first, second, and third ERO tertiles, respectively).

Despite the fact that bony erosion is considered "prototypic for RA," whereas joint space narrowing (which occurs in other disorders) is considered less characteristic of the disease, "in the present study we have been able to show that the clinical impact of joint destruction cartilage loss seems to be of much higher relevance than damage to the bone," Dr. Aletaha and his coauthors wrote.

"The data presented here provide sufficient evidence for developing, and further testing of, the hypothesis that cartilage damage, rather than bone destruction, may constitute the pivotal cause of physical functional impairment in RA," they concluded.

Data were provided by Abbott, Amgen, Centocor, Sanofi-Aventis and Wyeth (later acquired by Pfizer). None of the authors disclosed any personal competing interests in relation to this study.

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Major Finding: Joint space narrowing significantly corresponded with increasing disability in patients with rheumatoid arthritis.

Data Source: Pooled data from several clinical trials of patients in remission from rheumatoid arthritis.

Disclosures: Data were provided by Abbott, Amgen, Centocor, Sanofi-Aventis, and Wyeth (later acquired by Pfizer). None of the authors disclosed financial conflicts of interest in relation to this study.

Synovitis Persists Among RA Patients in 'Remission'

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Applying more stringent remission thresholds among rheumatoid arthritis patients lowered the percentage of those with lingering swollen and tender joints; however, the proportion of patients with synovitis on power Doppler ultrasound remained unchanged.

"Therefore, as clinical criteria cannot exclude the presence of active disease, the current remission criteria are more appropriate for defining low disease activity states," concluded Dr. Benazir Saleem in the May issue of Annals of the Rheumatic Diseases.

According to Dr. Saleem, patients who are currently judged by American College of Rheumatology and European League Against Rheumatism criteria to be in remission – with a DAS28 (disease activity score based on a 28-joints count) less than 2.6 – may still have tender and swollen joints, and corresponding structural progression of disease.

It may therefore be expected that more stringent criteria – that is, the use of lower cut-points for DAS28/SDAI (Simplified Disease Activity Index) to define remission – "would be associated with less ... imaging-detected synovitis," postulated Dr. Saleem, a clinical research fellow at the University of Leeds (England) and colleagues (Ann. Rheum. Dis. 2011;70:792-8).

"This would, for example, permit fewer (ideally zero) tender and swollen joints to be present in patients in remission, and thus there would be a better correlation with the absence of structural progression."

To test this theory, the researchers looked at 128 outpatients from the Chapel Allerton Hospital in Leeds who had DAS28 scores less than 2.6. Patients’ mean age was 54 years, and the median disease duration was 8 years.

All participants had been in remission for at least 6 months. Roughly half had achieved remission through the use of disease-modifying antirheumatic drugs; the remainder had been treated with combination tumor necrosis factor blocker and methotrexate (45% infliximab, 45% etanercept, and 10% adalimumab).

Overall, 31% of these patients who were classified as being in remission still had swollen joints, and 18% reported tender joints. More than half (51%) had synovitis that was detectable on power Doppler ultrasound, the "gold standard" of imaging for synovitis.

Dr. Saleem then divided patients into four subcategories: In all, 32 patients had a DAS28 less than 1.17; 31 had a score of 1.17-1.70; 32 patients registered a DAS28 of 1.71-2.03; and the remaining 33 had a DAS score greater than 2.03.

"As was to be expected, both swollen joint count in 28 joints [P less than .001] and tender joint count in 28 joints [P less than 0.001] decreased with decreasing DAS28," the investigators wrote.

However, the proportions of patients in imaging remission did not have a corresponding consistent decrease; indeed, only 9% of those in the lowest category were in strict imaging remission (defined as no joints showing synovitis in the dominant hand’s metacarpophalangeal joints 2-5, plus the wrist, according to grey scale and power Doppler ultrasound).

The stratification of patients into increasingly stringent SDAI categories resulted in a similar, predictable decrease in the number of swollen and tender joints as the score decreased. However, only 25% of those in the lowest SDAI category (score less than 1.51) were in strictly defined imaging remission.

"The use of the term remission in other areas of medicine implies the absence of active disease," wrote the authors. The rheumatologic equivalent of this true remission "would therefore not rely solely on clinical examination but would require imaging to confirm the absence of subclinical inflammation."

And although the widely used, easy-to-calculate DAS28 is a good tool, it is "insufficiently sensitive to exclude [clinically important] levels of inflammation," concluded the authors. They added that the relevance of this finding is not clear, since "the threshold level of ultrasound-determined inflammation that is of importance for subsequent clinical and radiographic progression has not yet been established."

Dr. Saleem and colleagues stated that they had no competing interests to declare in relation to this study.

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Applying more stringent remission thresholds among rheumatoid arthritis patients lowered the percentage of those with lingering swollen and tender joints; however, the proportion of patients with synovitis on power Doppler ultrasound remained unchanged.

"Therefore, as clinical criteria cannot exclude the presence of active disease, the current remission criteria are more appropriate for defining low disease activity states," concluded Dr. Benazir Saleem in the May issue of Annals of the Rheumatic Diseases.

According to Dr. Saleem, patients who are currently judged by American College of Rheumatology and European League Against Rheumatism criteria to be in remission – with a DAS28 (disease activity score based on a 28-joints count) less than 2.6 – may still have tender and swollen joints, and corresponding structural progression of disease.

It may therefore be expected that more stringent criteria – that is, the use of lower cut-points for DAS28/SDAI (Simplified Disease Activity Index) to define remission – "would be associated with less ... imaging-detected synovitis," postulated Dr. Saleem, a clinical research fellow at the University of Leeds (England) and colleagues (Ann. Rheum. Dis. 2011;70:792-8).

"This would, for example, permit fewer (ideally zero) tender and swollen joints to be present in patients in remission, and thus there would be a better correlation with the absence of structural progression."

To test this theory, the researchers looked at 128 outpatients from the Chapel Allerton Hospital in Leeds who had DAS28 scores less than 2.6. Patients’ mean age was 54 years, and the median disease duration was 8 years.

All participants had been in remission for at least 6 months. Roughly half had achieved remission through the use of disease-modifying antirheumatic drugs; the remainder had been treated with combination tumor necrosis factor blocker and methotrexate (45% infliximab, 45% etanercept, and 10% adalimumab).

Overall, 31% of these patients who were classified as being in remission still had swollen joints, and 18% reported tender joints. More than half (51%) had synovitis that was detectable on power Doppler ultrasound, the "gold standard" of imaging for synovitis.

Dr. Saleem then divided patients into four subcategories: In all, 32 patients had a DAS28 less than 1.17; 31 had a score of 1.17-1.70; 32 patients registered a DAS28 of 1.71-2.03; and the remaining 33 had a DAS score greater than 2.03.

"As was to be expected, both swollen joint count in 28 joints [P less than .001] and tender joint count in 28 joints [P less than 0.001] decreased with decreasing DAS28," the investigators wrote.

However, the proportions of patients in imaging remission did not have a corresponding consistent decrease; indeed, only 9% of those in the lowest category were in strict imaging remission (defined as no joints showing synovitis in the dominant hand’s metacarpophalangeal joints 2-5, plus the wrist, according to grey scale and power Doppler ultrasound).

The stratification of patients into increasingly stringent SDAI categories resulted in a similar, predictable decrease in the number of swollen and tender joints as the score decreased. However, only 25% of those in the lowest SDAI category (score less than 1.51) were in strictly defined imaging remission.

"The use of the term remission in other areas of medicine implies the absence of active disease," wrote the authors. The rheumatologic equivalent of this true remission "would therefore not rely solely on clinical examination but would require imaging to confirm the absence of subclinical inflammation."

And although the widely used, easy-to-calculate DAS28 is a good tool, it is "insufficiently sensitive to exclude [clinically important] levels of inflammation," concluded the authors. They added that the relevance of this finding is not clear, since "the threshold level of ultrasound-determined inflammation that is of importance for subsequent clinical and radiographic progression has not yet been established."

Dr. Saleem and colleagues stated that they had no competing interests to declare in relation to this study.

Applying more stringent remission thresholds among rheumatoid arthritis patients lowered the percentage of those with lingering swollen and tender joints; however, the proportion of patients with synovitis on power Doppler ultrasound remained unchanged.

"Therefore, as clinical criteria cannot exclude the presence of active disease, the current remission criteria are more appropriate for defining low disease activity states," concluded Dr. Benazir Saleem in the May issue of Annals of the Rheumatic Diseases.

According to Dr. Saleem, patients who are currently judged by American College of Rheumatology and European League Against Rheumatism criteria to be in remission – with a DAS28 (disease activity score based on a 28-joints count) less than 2.6 – may still have tender and swollen joints, and corresponding structural progression of disease.

It may therefore be expected that more stringent criteria – that is, the use of lower cut-points for DAS28/SDAI (Simplified Disease Activity Index) to define remission – "would be associated with less ... imaging-detected synovitis," postulated Dr. Saleem, a clinical research fellow at the University of Leeds (England) and colleagues (Ann. Rheum. Dis. 2011;70:792-8).

"This would, for example, permit fewer (ideally zero) tender and swollen joints to be present in patients in remission, and thus there would be a better correlation with the absence of structural progression."

To test this theory, the researchers looked at 128 outpatients from the Chapel Allerton Hospital in Leeds who had DAS28 scores less than 2.6. Patients’ mean age was 54 years, and the median disease duration was 8 years.

All participants had been in remission for at least 6 months. Roughly half had achieved remission through the use of disease-modifying antirheumatic drugs; the remainder had been treated with combination tumor necrosis factor blocker and methotrexate (45% infliximab, 45% etanercept, and 10% adalimumab).

Overall, 31% of these patients who were classified as being in remission still had swollen joints, and 18% reported tender joints. More than half (51%) had synovitis that was detectable on power Doppler ultrasound, the "gold standard" of imaging for synovitis.

Dr. Saleem then divided patients into four subcategories: In all, 32 patients had a DAS28 less than 1.17; 31 had a score of 1.17-1.70; 32 patients registered a DAS28 of 1.71-2.03; and the remaining 33 had a DAS score greater than 2.03.

"As was to be expected, both swollen joint count in 28 joints [P less than .001] and tender joint count in 28 joints [P less than 0.001] decreased with decreasing DAS28," the investigators wrote.

However, the proportions of patients in imaging remission did not have a corresponding consistent decrease; indeed, only 9% of those in the lowest category were in strict imaging remission (defined as no joints showing synovitis in the dominant hand’s metacarpophalangeal joints 2-5, plus the wrist, according to grey scale and power Doppler ultrasound).

The stratification of patients into increasingly stringent SDAI categories resulted in a similar, predictable decrease in the number of swollen and tender joints as the score decreased. However, only 25% of those in the lowest SDAI category (score less than 1.51) were in strictly defined imaging remission.

"The use of the term remission in other areas of medicine implies the absence of active disease," wrote the authors. The rheumatologic equivalent of this true remission "would therefore not rely solely on clinical examination but would require imaging to confirm the absence of subclinical inflammation."

And although the widely used, easy-to-calculate DAS28 is a good tool, it is "insufficiently sensitive to exclude [clinically important] levels of inflammation," concluded the authors. They added that the relevance of this finding is not clear, since "the threshold level of ultrasound-determined inflammation that is of importance for subsequent clinical and radiographic progression has not yet been established."

Dr. Saleem and colleagues stated that they had no competing interests to declare in relation to this study.

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Synovitis Persists Among RA Patients in 'Remission'
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Major Finding: Among RA patients in remission, only 9% with DAS28 scores less than 1.17 were found to be free of synovitis on power Doppler imaging; among patients with correspondingly low SDAI scores, just 25% had similarly clear scans, with the remainder showing some degree of inflammation.

Data Source: A cohort of 128 outpatients seen at a clinic in Leeds, England.

Disclosures: The authors stated that they had no competing interests to declare in relation to this study.

Synovitis Persists Among RA Patients in 'Remission'

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Synovitis Persists Among RA Patients in 'Remission'

Applying more stringent remission thresholds among rheumatoid arthritis patients lowered the percentage of those with lingering swollen and tender joints; however, the proportion of patients with synovitis on power Doppler ultrasound remained unchanged.

"Therefore, as clinical criteria cannot exclude the presence of active disease, the current remission criteria are more appropriate for defining low disease activity states," concluded Dr. Benazir Saleem in the May issue of Annals of the Rheumatic Diseases.

According to Dr. Saleem, patients who are currently judged by American College of Rheumatology and European League Against Rheumatism criteria to be in remission – with a DAS28 (disease activity score based on a 28-joints count) less than 2.6 – may still have tender and swollen joints, and corresponding structural progression of disease.

It may therefore be expected that more stringent criteria – that is, the use of lower cut-points for DAS28/SDAI (Simplified Disease Activity Index) to define remission – "would be associated with less ... imaging-detected synovitis," postulated Dr. Saleem, a clinical research fellow at the University of Leeds (England) and colleagues (Ann. Rheum. Dis. 2011;70:792-8).

"This would, for example, permit fewer (ideally zero) tender and swollen joints to be present in patients in remission, and thus there would be a better correlation with the absence of structural progression."

To test this theory, the researchers looked at 128 outpatients from the Chapel Allerton Hospital in Leeds who had DAS28 scores less than 2.6. Patients’ mean age was 54 years, and the median disease duration was 8 years.

All participants had been in remission for at least 6 months. Roughly half had achieved remission through the use of disease-modifying antirheumatic drugs; the remainder had been treated with combination tumor necrosis factor blocker and methotrexate (45% infliximab, 45% etanercept, and 10% adalimumab).

Overall, 31% of these patients who were classified as being in remission still had swollen joints, and 18% reported tender joints. More than half (51%) had synovitis that was detectable on power Doppler ultrasound, the "gold standard" of imaging for synovitis.

Dr. Saleem then divided patients into four subcategories: In all, 32 patients had a DAS28 less than 1.17; 31 had a score of 1.17-1.70; 32 patients registered a DAS28 of 1.71-2.03; and the remaining 33 had a DAS score greater than 2.03.

"As was to be expected, both swollen joint count in 28 joints [P less than .001] and tender joint count in 28 joints [P less than 0.001] decreased with decreasing DAS28," the investigators wrote.

However, the proportions of patients in imaging remission did not have a corresponding consistent decrease; indeed, only 9% of those in the lowest category were in strict imaging remission (defined as no joints showing synovitis in the dominant hand’s metacarpophalangeal joints 2-5, plus the wrist, according to grey scale and power Doppler ultrasound).

The stratification of patients into increasingly stringent SDAI categories resulted in a similar, predictable decrease in the number of swollen and tender joints as the score decreased. However, only 25% of those in the lowest SDAI category (score less than 1.51) were in strictly defined imaging remission.

"The use of the term remission in other areas of medicine implies the absence of active disease," wrote the authors. The rheumatologic equivalent of this true remission "would therefore not rely solely on clinical examination but would require imaging to confirm the absence of subclinical inflammation."

And although the widely used, easy-to-calculate DAS28 is a good tool, it is "insufficiently sensitive to exclude [clinically important] levels of inflammation," concluded the authors. They added that the relevance of this finding is not clear, since "the threshold level of ultrasound-determined inflammation that is of importance for subsequent clinical and radiographic progression has not yet been established."

Dr. Saleem and colleagues stated that they had no competing interests to declare in relation to this study.

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Applying more stringent remission thresholds among rheumatoid arthritis patients lowered the percentage of those with lingering swollen and tender joints; however, the proportion of patients with synovitis on power Doppler ultrasound remained unchanged.

"Therefore, as clinical criteria cannot exclude the presence of active disease, the current remission criteria are more appropriate for defining low disease activity states," concluded Dr. Benazir Saleem in the May issue of Annals of the Rheumatic Diseases.

According to Dr. Saleem, patients who are currently judged by American College of Rheumatology and European League Against Rheumatism criteria to be in remission – with a DAS28 (disease activity score based on a 28-joints count) less than 2.6 – may still have tender and swollen joints, and corresponding structural progression of disease.

It may therefore be expected that more stringent criteria – that is, the use of lower cut-points for DAS28/SDAI (Simplified Disease Activity Index) to define remission – "would be associated with less ... imaging-detected synovitis," postulated Dr. Saleem, a clinical research fellow at the University of Leeds (England) and colleagues (Ann. Rheum. Dis. 2011;70:792-8).

"This would, for example, permit fewer (ideally zero) tender and swollen joints to be present in patients in remission, and thus there would be a better correlation with the absence of structural progression."

To test this theory, the researchers looked at 128 outpatients from the Chapel Allerton Hospital in Leeds who had DAS28 scores less than 2.6. Patients’ mean age was 54 years, and the median disease duration was 8 years.

All participants had been in remission for at least 6 months. Roughly half had achieved remission through the use of disease-modifying antirheumatic drugs; the remainder had been treated with combination tumor necrosis factor blocker and methotrexate (45% infliximab, 45% etanercept, and 10% adalimumab).

Overall, 31% of these patients who were classified as being in remission still had swollen joints, and 18% reported tender joints. More than half (51%) had synovitis that was detectable on power Doppler ultrasound, the "gold standard" of imaging for synovitis.

Dr. Saleem then divided patients into four subcategories: In all, 32 patients had a DAS28 less than 1.17; 31 had a score of 1.17-1.70; 32 patients registered a DAS28 of 1.71-2.03; and the remaining 33 had a DAS score greater than 2.03.

"As was to be expected, both swollen joint count in 28 joints [P less than .001] and tender joint count in 28 joints [P less than 0.001] decreased with decreasing DAS28," the investigators wrote.

However, the proportions of patients in imaging remission did not have a corresponding consistent decrease; indeed, only 9% of those in the lowest category were in strict imaging remission (defined as no joints showing synovitis in the dominant hand’s metacarpophalangeal joints 2-5, plus the wrist, according to grey scale and power Doppler ultrasound).

The stratification of patients into increasingly stringent SDAI categories resulted in a similar, predictable decrease in the number of swollen and tender joints as the score decreased. However, only 25% of those in the lowest SDAI category (score less than 1.51) were in strictly defined imaging remission.

"The use of the term remission in other areas of medicine implies the absence of active disease," wrote the authors. The rheumatologic equivalent of this true remission "would therefore not rely solely on clinical examination but would require imaging to confirm the absence of subclinical inflammation."

And although the widely used, easy-to-calculate DAS28 is a good tool, it is "insufficiently sensitive to exclude [clinically important] levels of inflammation," concluded the authors. They added that the relevance of this finding is not clear, since "the threshold level of ultrasound-determined inflammation that is of importance for subsequent clinical and radiographic progression has not yet been established."

Dr. Saleem and colleagues stated that they had no competing interests to declare in relation to this study.

Applying more stringent remission thresholds among rheumatoid arthritis patients lowered the percentage of those with lingering swollen and tender joints; however, the proportion of patients with synovitis on power Doppler ultrasound remained unchanged.

"Therefore, as clinical criteria cannot exclude the presence of active disease, the current remission criteria are more appropriate for defining low disease activity states," concluded Dr. Benazir Saleem in the May issue of Annals of the Rheumatic Diseases.

According to Dr. Saleem, patients who are currently judged by American College of Rheumatology and European League Against Rheumatism criteria to be in remission – with a DAS28 (disease activity score based on a 28-joints count) less than 2.6 – may still have tender and swollen joints, and corresponding structural progression of disease.

It may therefore be expected that more stringent criteria – that is, the use of lower cut-points for DAS28/SDAI (Simplified Disease Activity Index) to define remission – "would be associated with less ... imaging-detected synovitis," postulated Dr. Saleem, a clinical research fellow at the University of Leeds (England) and colleagues (Ann. Rheum. Dis. 2011;70:792-8).

"This would, for example, permit fewer (ideally zero) tender and swollen joints to be present in patients in remission, and thus there would be a better correlation with the absence of structural progression."

To test this theory, the researchers looked at 128 outpatients from the Chapel Allerton Hospital in Leeds who had DAS28 scores less than 2.6. Patients’ mean age was 54 years, and the median disease duration was 8 years.

All participants had been in remission for at least 6 months. Roughly half had achieved remission through the use of disease-modifying antirheumatic drugs; the remainder had been treated with combination tumor necrosis factor blocker and methotrexate (45% infliximab, 45% etanercept, and 10% adalimumab).

Overall, 31% of these patients who were classified as being in remission still had swollen joints, and 18% reported tender joints. More than half (51%) had synovitis that was detectable on power Doppler ultrasound, the "gold standard" of imaging for synovitis.

Dr. Saleem then divided patients into four subcategories: In all, 32 patients had a DAS28 less than 1.17; 31 had a score of 1.17-1.70; 32 patients registered a DAS28 of 1.71-2.03; and the remaining 33 had a DAS score greater than 2.03.

"As was to be expected, both swollen joint count in 28 joints [P less than .001] and tender joint count in 28 joints [P less than 0.001] decreased with decreasing DAS28," the investigators wrote.

However, the proportions of patients in imaging remission did not have a corresponding consistent decrease; indeed, only 9% of those in the lowest category were in strict imaging remission (defined as no joints showing synovitis in the dominant hand’s metacarpophalangeal joints 2-5, plus the wrist, according to grey scale and power Doppler ultrasound).

The stratification of patients into increasingly stringent SDAI categories resulted in a similar, predictable decrease in the number of swollen and tender joints as the score decreased. However, only 25% of those in the lowest SDAI category (score less than 1.51) were in strictly defined imaging remission.

"The use of the term remission in other areas of medicine implies the absence of active disease," wrote the authors. The rheumatologic equivalent of this true remission "would therefore not rely solely on clinical examination but would require imaging to confirm the absence of subclinical inflammation."

And although the widely used, easy-to-calculate DAS28 is a good tool, it is "insufficiently sensitive to exclude [clinically important] levels of inflammation," concluded the authors. They added that the relevance of this finding is not clear, since "the threshold level of ultrasound-determined inflammation that is of importance for subsequent clinical and radiographic progression has not yet been established."

Dr. Saleem and colleagues stated that they had no competing interests to declare in relation to this study.

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Major Finding: Among RA patients in remission, only 9% with DAS28 scores less than 1.17 were found to be free of synovitis on power Doppler imaging; among patients with correspondingly low SDAI scores, just 25% had similarly clear scans, with the remainder showing some degree of inflammation.

Data Source: A cohort of 128 outpatients seen at a clinic in Leeds, England.

Disclosures: The authors stated that they had no competing interests to declare in relation to this study.

Study: Be Cautious When Using Anti-TNFs in Pregnancy

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Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, are from the “largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy” to date, according to the authors. However, the study was unable to control for the possibility that disease severity itself plays a role in adverse pregnancy outcomes.

Nevertheless, “no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain,” recommended Dr. Suzanne M.M. Verstappen of the University of Manchester's Arthritis Research UK Epidemiology Unit, and her colleagues. They looked at women who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs. A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb). Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post 20 weeks). There was also one neonatal death registered. The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death. Among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

The British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. The authors added that they had no personal competing interests in relation to this study. The society also receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

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Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, are from the “largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy” to date, according to the authors. However, the study was unable to control for the possibility that disease severity itself plays a role in adverse pregnancy outcomes.

Nevertheless, “no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain,” recommended Dr. Suzanne M.M. Verstappen of the University of Manchester's Arthritis Research UK Epidemiology Unit, and her colleagues. They looked at women who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs. A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb). Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post 20 weeks). There was also one neonatal death registered. The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death. Among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

The British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. The authors added that they had no personal competing interests in relation to this study. The society also receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data, culled from the British Society for Rheumatology Biologics Registry, are from the “largest detailed prospective collection of pregnancy outcomes in women with arthritis-related diseases exposed to anti-TNF therapy” to date, according to the authors. However, the study was unable to control for the possibility that disease severity itself plays a role in adverse pregnancy outcomes.

Nevertheless, “no firm conclusions can be drawn about the safety of anti-TNF therapy during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception must remain,” recommended Dr. Suzanne M.M. Verstappen of the University of Manchester's Arthritis Research UK Epidemiology Unit, and her colleagues. They looked at women who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception. A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs. A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use, but rather received nonbiological disease-modifying antirheumatic drugs (DMARDs), excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb). Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies. They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%) and 2 intrauterine deaths (occurring post 20 weeks). There was also one neonatal death registered. The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: the 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%). There were two intrauterine deaths, including the twin death. Among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were zero terminations and one spontaneous abortion (10%).

The British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Shering-Plough, Wyeth Pharmaceuticals, and Roche. The authors added that they had no personal competing interests in relation to this study. The society also receives funding from several pharmaceutical companies, including the makers of anti-TNFs.

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Synovitis Persists in RA Patients in 'Remission'

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Major Finding: Among RA patients in remission, only 9% with DAS28 scores less than 1.17 were found to be free of synovitis on power Doppler imaging; among patients with correspondingly low SDAI scores, just 25% had similarly clear scans, with the remainder showing some degree of inflammation.

Data Source: A cohort of 128 outpatients seen at a clinic in Leeds, England.

Disclosures: The authors stated that they had no competing interests to declare in relation to this study.

Applying more stringent remission thresholds among rheumatoid arthritis patients lowered the percentage of those with lingering swollen and tender joints; however, the proportion of patients with synovitis on power Doppler ultrasound remained unchanged.

“Therefore, as clinical criteria cannot exclude the presence of active disease, the current remission criteria are more appropriate for defining low disease activity states,” concluded Dr. Benazir Saleem and colleagues.

According to the investigators, patients who are currently judged by American College of Rheumatology and European League Against Rheumatism criteria to be in remission – with a DAS28 (disease activity score based on a 28-joints count) less than 2.6 – may still have tender and swollen joints, and corresponding structural progression of disease.

It may therefore be expected that more stringent criteria – that is, the use of lower cut-points for DAS28/SDAI (Simplified Disease Activity Index) to define remission – “would be associated with less … imaging-detected synovitis,” postulated Dr. Saleem, a clinical research fellow at the University of Leeds (England) and colleagues (Ann. Rheum. Dis. 2011;70:792–8).

“This would, for example, permit fewer (ideally zero) tender and swollen joints to be present in patients in remission, and thus there would be a better correlation with the absence of structural progression,” according to Dr. Saleem and coauthors.

To test this theory, the researchers looked at 128 outpatients from the Chapel Allerton Hospital in Leeds who had DAS28 scores less than 2.6. Patients' mean age was 54 years, and the median disease duration was 8 years.

All study participants had been in remission for a period of at least 6 months. Roughly half of them had achieved remission through the use of disease-modifying antirheumatic drugs; the remainder had been treated with a regimen consisting of combination tumor necrosis factor blocker and methotrexate (45% infliximab, 45% etanercept, and 10% adalimumab).

Overall, a total of 31% of these patients who were classified as being in remission still had swollen joints, and 18% reported tender joints. In addition, more than half of the patients (51%) had synovitis that was detectable on power Doppler ultrasound, which is considered the “gold standard” of imaging for synovitis.

Dr. Saleem then divided the patients into four subcategories: In all, 32 patients had a DAS28 less than 1.17; 31 had a score of 1.17–1.70; 32 patients registered a DAS28 of 1.71–2.03; and the remaining 33 patients had a DAS score greater than 2.03.

“As was to be expected, both swollen joint count in 28 joints [P less than .001] and tender joint count in 28 joints [P less than 0.001] decreased with decreasing DAS28,” Dr. Saleem and coinvestigators wrote.

However, the proportions of patients in imaging remission did not have a corresponding consistent decrease; indeed, only 9% of those in the lowest category were in strict imaging remission (defined as no joints showing synovitis in the dominant hand's metacarpophalangeal joints 2–5, plus the wrist, according to gray scale and power Doppler ultrasound).

The stratification of the study participants into increasingly stringent SDAI categories resulted in a similar, predictable decrease in the number of swollen and tender joints as the score decreased.

However, only 25% of those in the lowest SDAI category (score less than 1.51) were in strictly defined imaging remission.

“The use of the term remission in other areas of medicine implies the absence of active disease,” wrote the researchers.

The rheumatologic equivalent of this true remission “would therefore not rely solely on clinical examination but would require imaging to confirm the absence of subclinical inflammation,” according to Dr. Saleem and coinvestigators.

And although the widely used, easy-to-calculate DAS28 is a good tool, it is “insufficiently sensitive to exclude [clinically important] levels of inflammation,” they concluded.

The relevance of this finding is not clear, because “the threshold level of ultrasound-determined inflammation that is of importance for subsequent clinical and radiographic progression has not yet been established,” according to the investigators.

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Major Finding: Among RA patients in remission, only 9% with DAS28 scores less than 1.17 were found to be free of synovitis on power Doppler imaging; among patients with correspondingly low SDAI scores, just 25% had similarly clear scans, with the remainder showing some degree of inflammation.

Data Source: A cohort of 128 outpatients seen at a clinic in Leeds, England.

Disclosures: The authors stated that they had no competing interests to declare in relation to this study.

Applying more stringent remission thresholds among rheumatoid arthritis patients lowered the percentage of those with lingering swollen and tender joints; however, the proportion of patients with synovitis on power Doppler ultrasound remained unchanged.

“Therefore, as clinical criteria cannot exclude the presence of active disease, the current remission criteria are more appropriate for defining low disease activity states,” concluded Dr. Benazir Saleem and colleagues.

According to the investigators, patients who are currently judged by American College of Rheumatology and European League Against Rheumatism criteria to be in remission – with a DAS28 (disease activity score based on a 28-joints count) less than 2.6 – may still have tender and swollen joints, and corresponding structural progression of disease.

It may therefore be expected that more stringent criteria – that is, the use of lower cut-points for DAS28/SDAI (Simplified Disease Activity Index) to define remission – “would be associated with less … imaging-detected synovitis,” postulated Dr. Saleem, a clinical research fellow at the University of Leeds (England) and colleagues (Ann. Rheum. Dis. 2011;70:792–8).

“This would, for example, permit fewer (ideally zero) tender and swollen joints to be present in patients in remission, and thus there would be a better correlation with the absence of structural progression,” according to Dr. Saleem and coauthors.

To test this theory, the researchers looked at 128 outpatients from the Chapel Allerton Hospital in Leeds who had DAS28 scores less than 2.6. Patients' mean age was 54 years, and the median disease duration was 8 years.

All study participants had been in remission for a period of at least 6 months. Roughly half of them had achieved remission through the use of disease-modifying antirheumatic drugs; the remainder had been treated with a regimen consisting of combination tumor necrosis factor blocker and methotrexate (45% infliximab, 45% etanercept, and 10% adalimumab).

Overall, a total of 31% of these patients who were classified as being in remission still had swollen joints, and 18% reported tender joints. In addition, more than half of the patients (51%) had synovitis that was detectable on power Doppler ultrasound, which is considered the “gold standard” of imaging for synovitis.

Dr. Saleem then divided the patients into four subcategories: In all, 32 patients had a DAS28 less than 1.17; 31 had a score of 1.17–1.70; 32 patients registered a DAS28 of 1.71–2.03; and the remaining 33 patients had a DAS score greater than 2.03.

“As was to be expected, both swollen joint count in 28 joints [P less than .001] and tender joint count in 28 joints [P less than 0.001] decreased with decreasing DAS28,” Dr. Saleem and coinvestigators wrote.

However, the proportions of patients in imaging remission did not have a corresponding consistent decrease; indeed, only 9% of those in the lowest category were in strict imaging remission (defined as no joints showing synovitis in the dominant hand's metacarpophalangeal joints 2–5, plus the wrist, according to gray scale and power Doppler ultrasound).

The stratification of the study participants into increasingly stringent SDAI categories resulted in a similar, predictable decrease in the number of swollen and tender joints as the score decreased.

However, only 25% of those in the lowest SDAI category (score less than 1.51) were in strictly defined imaging remission.

“The use of the term remission in other areas of medicine implies the absence of active disease,” wrote the researchers.

The rheumatologic equivalent of this true remission “would therefore not rely solely on clinical examination but would require imaging to confirm the absence of subclinical inflammation,” according to Dr. Saleem and coinvestigators.

And although the widely used, easy-to-calculate DAS28 is a good tool, it is “insufficiently sensitive to exclude [clinically important] levels of inflammation,” they concluded.

The relevance of this finding is not clear, because “the threshold level of ultrasound-determined inflammation that is of importance for subsequent clinical and radiographic progression has not yet been established,” according to the investigators.

Major Finding: Among RA patients in remission, only 9% with DAS28 scores less than 1.17 were found to be free of synovitis on power Doppler imaging; among patients with correspondingly low SDAI scores, just 25% had similarly clear scans, with the remainder showing some degree of inflammation.

Data Source: A cohort of 128 outpatients seen at a clinic in Leeds, England.

Disclosures: The authors stated that they had no competing interests to declare in relation to this study.

Applying more stringent remission thresholds among rheumatoid arthritis patients lowered the percentage of those with lingering swollen and tender joints; however, the proportion of patients with synovitis on power Doppler ultrasound remained unchanged.

“Therefore, as clinical criteria cannot exclude the presence of active disease, the current remission criteria are more appropriate for defining low disease activity states,” concluded Dr. Benazir Saleem and colleagues.

According to the investigators, patients who are currently judged by American College of Rheumatology and European League Against Rheumatism criteria to be in remission – with a DAS28 (disease activity score based on a 28-joints count) less than 2.6 – may still have tender and swollen joints, and corresponding structural progression of disease.

It may therefore be expected that more stringent criteria – that is, the use of lower cut-points for DAS28/SDAI (Simplified Disease Activity Index) to define remission – “would be associated with less … imaging-detected synovitis,” postulated Dr. Saleem, a clinical research fellow at the University of Leeds (England) and colleagues (Ann. Rheum. Dis. 2011;70:792–8).

“This would, for example, permit fewer (ideally zero) tender and swollen joints to be present in patients in remission, and thus there would be a better correlation with the absence of structural progression,” according to Dr. Saleem and coauthors.

To test this theory, the researchers looked at 128 outpatients from the Chapel Allerton Hospital in Leeds who had DAS28 scores less than 2.6. Patients' mean age was 54 years, and the median disease duration was 8 years.

All study participants had been in remission for a period of at least 6 months. Roughly half of them had achieved remission through the use of disease-modifying antirheumatic drugs; the remainder had been treated with a regimen consisting of combination tumor necrosis factor blocker and methotrexate (45% infliximab, 45% etanercept, and 10% adalimumab).

Overall, a total of 31% of these patients who were classified as being in remission still had swollen joints, and 18% reported tender joints. In addition, more than half of the patients (51%) had synovitis that was detectable on power Doppler ultrasound, which is considered the “gold standard” of imaging for synovitis.

Dr. Saleem then divided the patients into four subcategories: In all, 32 patients had a DAS28 less than 1.17; 31 had a score of 1.17–1.70; 32 patients registered a DAS28 of 1.71–2.03; and the remaining 33 patients had a DAS score greater than 2.03.

“As was to be expected, both swollen joint count in 28 joints [P less than .001] and tender joint count in 28 joints [P less than 0.001] decreased with decreasing DAS28,” Dr. Saleem and coinvestigators wrote.

However, the proportions of patients in imaging remission did not have a corresponding consistent decrease; indeed, only 9% of those in the lowest category were in strict imaging remission (defined as no joints showing synovitis in the dominant hand's metacarpophalangeal joints 2–5, plus the wrist, according to gray scale and power Doppler ultrasound).

The stratification of the study participants into increasingly stringent SDAI categories resulted in a similar, predictable decrease in the number of swollen and tender joints as the score decreased.

However, only 25% of those in the lowest SDAI category (score less than 1.51) were in strictly defined imaging remission.

“The use of the term remission in other areas of medicine implies the absence of active disease,” wrote the researchers.

The rheumatologic equivalent of this true remission “would therefore not rely solely on clinical examination but would require imaging to confirm the absence of subclinical inflammation,” according to Dr. Saleem and coinvestigators.

And although the widely used, easy-to-calculate DAS28 is a good tool, it is “insufficiently sensitive to exclude [clinically important] levels of inflammation,” they concluded.

The relevance of this finding is not clear, because “the threshold level of ultrasound-determined inflammation that is of importance for subsequent clinical and radiographic progression has not yet been established,” according to the investigators.

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Anti-TNFs Use in Pregnancy Still Requires Caution

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Anti-TNFs Use in Pregnancy Still Requires Caution

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data were culled from the British Society for Rheumatology Biologics Register.

Despite its relatively large size, the study was unable to control for the looming possibility that disease severity itself plays a role in adverse pregnancy outcomes, the authors said.

“[W]ithout further evidence, guidelines that suggest these drugs should be avoided at the time of conception must remain” in place, recommended Dr. Suzanne M.M. Verstappen of the University of Manchester's Arthritis Research UK Epidemiology Unit, and her associates.

The investigators looked at women in the register who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception.

A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs, two drugs with a “known risk of adverse pregnancy outcomes,” according to the authors.

A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use but rather received nonbiologic disease-modifying antirheumatic drugs, excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822]).

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb).

Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies.

They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%), and 2 intrauterine deaths (occurring post-20 weeks).

There was also one neonatal death registered.

The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: The 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%).

There were two intrauterine deaths, including the twin death.

Finally, among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were 0 terminations and 1 spontaneous abortion (10%).

The baseline disease activity score–28 (DAS28) was significantly higher in the anti-TNF cohorts, vs. cohort III: 6.5, 6.1, and 6.0 in cohorts Ia, Ib, and II, respectively, vs. 5.1 in cohort III.

Dr. H. Michael Belmont, medical director of New York University's Hospital for Joint Diseases, as well as the director of the lupus clinic at Bellevue Hospital, New York, commented that, until more data are available, “The default choice would be to avoid these drugs during pregnancy. Starting their use in a women contemplating conception should be delayed based on the data on hand.”

The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Roche, Shering-Plough, and Wyeth Pharmaceuticals.

They added that they had no personal competing interests in relation to this study.

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What I Tell My Pregnant Patients

The only way to definitively address the question of risk associated with anti-TNFs and pregnancy would be to conduct a randomized controlled trial, according to Dr. Deborah P.M. Symmons.

There are, however, a few problems with that strategy. “Clearly, this would be very difficult to design, would need to be very large, and is never going to happen!” she joked.

“Beyond that, we have to wait for anecdotal evidence to accumulate.”

In the meantime, she said, “We advise all patients with rheumatoid arthritis to discuss a planned pregnancy with their rheumatologist prior to conception in order to make prospective plans about what to do about treatment. There are a number of other antirheumatic drugs, for example methotrexate and leflunomide, which carry a substantially higher risk than has been seen with anti-TNF therapy so far. However, many patients on anti-TNFs take them with another anti-rheumatic drug.”

According to Dr. Symmons, when treating a female patient of child-bearing age, “I would share what is currently known about the risks and benefits of continuing anti-TNF therapy with the woman with RA and let her ask further questions and make up her own mind about what to do.

“This study is reassuring for us to continue our current practice.”

DR. SYMMONS is one of the authors of the current study as well as a professor of rheumatology and musculoskeletal epidemiology at the University of Manchester, England. She had no financial interests to disclose.

 

 

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Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data were culled from the British Society for Rheumatology Biologics Register.

Despite its relatively large size, the study was unable to control for the looming possibility that disease severity itself plays a role in adverse pregnancy outcomes, the authors said.

“[W]ithout further evidence, guidelines that suggest these drugs should be avoided at the time of conception must remain” in place, recommended Dr. Suzanne M.M. Verstappen of the University of Manchester's Arthritis Research UK Epidemiology Unit, and her associates.

The investigators looked at women in the register who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception.

A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs, two drugs with a “known risk of adverse pregnancy outcomes,” according to the authors.

A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use but rather received nonbiologic disease-modifying antirheumatic drugs, excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822]).

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb).

Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies.

They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%), and 2 intrauterine deaths (occurring post-20 weeks).

There was also one neonatal death registered.

The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: The 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%).

There were two intrauterine deaths, including the twin death.

Finally, among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were 0 terminations and 1 spontaneous abortion (10%).

The baseline disease activity score–28 (DAS28) was significantly higher in the anti-TNF cohorts, vs. cohort III: 6.5, 6.1, and 6.0 in cohorts Ia, Ib, and II, respectively, vs. 5.1 in cohort III.

Dr. H. Michael Belmont, medical director of New York University's Hospital for Joint Diseases, as well as the director of the lupus clinic at Bellevue Hospital, New York, commented that, until more data are available, “The default choice would be to avoid these drugs during pregnancy. Starting their use in a women contemplating conception should be delayed based on the data on hand.”

The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Roche, Shering-Plough, and Wyeth Pharmaceuticals.

They added that they had no personal competing interests in relation to this study.

View on the News

What I Tell My Pregnant Patients

The only way to definitively address the question of risk associated with anti-TNFs and pregnancy would be to conduct a randomized controlled trial, according to Dr. Deborah P.M. Symmons.

There are, however, a few problems with that strategy. “Clearly, this would be very difficult to design, would need to be very large, and is never going to happen!” she joked.

“Beyond that, we have to wait for anecdotal evidence to accumulate.”

In the meantime, she said, “We advise all patients with rheumatoid arthritis to discuss a planned pregnancy with their rheumatologist prior to conception in order to make prospective plans about what to do about treatment. There are a number of other antirheumatic drugs, for example methotrexate and leflunomide, which carry a substantially higher risk than has been seen with anti-TNF therapy so far. However, many patients on anti-TNFs take them with another anti-rheumatic drug.”

According to Dr. Symmons, when treating a female patient of child-bearing age, “I would share what is currently known about the risks and benefits of continuing anti-TNF therapy with the woman with RA and let her ask further questions and make up her own mind about what to do.

“This study is reassuring for us to continue our current practice.”

DR. SYMMONS is one of the authors of the current study as well as a professor of rheumatology and musculoskeletal epidemiology at the University of Manchester, England. She had no financial interests to disclose.

 

 

Vitals

Pregnant women taking tumor necrosis factor inhibitors at conception experienced a higher rate of spontaneous abortion than did patients who did not.

The data were culled from the British Society for Rheumatology Biologics Register.

Despite its relatively large size, the study was unable to control for the looming possibility that disease severity itself plays a role in adverse pregnancy outcomes, the authors said.

“[W]ithout further evidence, guidelines that suggest these drugs should be avoided at the time of conception must remain” in place, recommended Dr. Suzanne M.M. Verstappen of the University of Manchester's Arthritis Research UK Epidemiology Unit, and her associates.

The investigators looked at women in the register who received adalimumab, etanercept, or infliximab either at conception or at any time prior to conception.

A subset was also exposed to methotrexate and/or leflunomide at time of conception in addition to the anti-TNFs, two drugs with a “known risk of adverse pregnancy outcomes,” according to the authors.

A fourth cohort with active rheumatoid arthritis had no history of anti-TNF use but rather received nonbiologic disease-modifying antirheumatic drugs, excluding methotrexate and leflunomide (Ann. Rheum. Dis. 2011 [doi:10.1136/ard.2010.140822]).

Among cohort Ia, which included 20 women (21 pregnancies) who took anti-TNFs plus either methotrexate and/or leflunomide at conception, there were 10 live births, 4 terminations, and 7 (33%) spontaneous abortions (miscarriages occurring prior to 20 weeks or to viability outside the womb).

Among cohort Ib, which included 44 women who took anti-TNFs at conception, but not methotrexate or leflunomide, there were 50 pregnancies.

They included 32 live births among this cohort, 4 terminations, 12 spontaneous abortions (24%), and 2 intrauterine deaths (occurring post-20 weeks).

There was also one neonatal death registered.

The women who had taken anti-TNFs in the past, but not at the time of conception (cohort II), did have seemingly better outcomes: The 59 pregnancies (54 women) resulted in live births in 46 cases (including one of two twins), terminations in 2, and spontaneous abortions in 10 (17%).

There were two intrauterine deaths, including the twin death.

Finally, among the 10 pregnancies in 10 women who had no history of anti-TNF use (cohort III), there were 0 terminations and 1 spontaneous abortion (10%).

The baseline disease activity score–28 (DAS28) was significantly higher in the anti-TNF cohorts, vs. cohort III: 6.5, 6.1, and 6.0 in cohorts Ia, Ib, and II, respectively, vs. 5.1 in cohort III.

Dr. H. Michael Belmont, medical director of New York University's Hospital for Joint Diseases, as well as the director of the lupus clinic at Bellevue Hospital, New York, commented that, until more data are available, “The default choice would be to avoid these drugs during pregnancy. Starting their use in a women contemplating conception should be delayed based on the data on hand.”

The study investigators disclosed that the British Society for Rheumatology receives restricted income from Abbott Laboratories, Biovitrum, Roche, Shering-Plough, and Wyeth Pharmaceuticals.

They added that they had no personal competing interests in relation to this study.

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What I Tell My Pregnant Patients

The only way to definitively address the question of risk associated with anti-TNFs and pregnancy would be to conduct a randomized controlled trial, according to Dr. Deborah P.M. Symmons.

There are, however, a few problems with that strategy. “Clearly, this would be very difficult to design, would need to be very large, and is never going to happen!” she joked.

“Beyond that, we have to wait for anecdotal evidence to accumulate.”

In the meantime, she said, “We advise all patients with rheumatoid arthritis to discuss a planned pregnancy with their rheumatologist prior to conception in order to make prospective plans about what to do about treatment. There are a number of other antirheumatic drugs, for example methotrexate and leflunomide, which carry a substantially higher risk than has been seen with anti-TNF therapy so far. However, many patients on anti-TNFs take them with another anti-rheumatic drug.”

According to Dr. Symmons, when treating a female patient of child-bearing age, “I would share what is currently known about the risks and benefits of continuing anti-TNF therapy with the woman with RA and let her ask further questions and make up her own mind about what to do.

“This study is reassuring for us to continue our current practice.”

DR. SYMMONS is one of the authors of the current study as well as a professor of rheumatology and musculoskeletal epidemiology at the University of Manchester, England. She had no financial interests to disclose.

 

 

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