Canadian Rheumatology Association (CRA): Scientific Conference and Annual General Meeting

VICTORIA, B.C. – Subclinical enthesitis occurs more commonly in patients with psoriatic arthritis than in those with psoriasis, possibly as a result of age and obesity rather than disease severity, to judge from the findings of a cross-sectional study conducted by investigators at Toronto Western Hospital.

The investigators used ultrasound as well as clinical examination to assess the extent, if any, of enthesitis in study participants, who were 59 patients with psoriatic arthritis and 79 patients with psoriasis. Study participants were recruited from longitudinal cohorts. The control group was made up of 60 healthy volunteers who did not have any personal or family history of spondyloarthropathy. They were evaluated for enthesitis at sites in the calcaneus, knee, and olecranon.

Findings on ultrasound – any enthesophytes, bony erosions, tendon thickness, and bursitis, within tendons – were scored using GUESS (Glasgow Ultrasound Enthesitis Scoring System), which reflects the overall burden bilaterally of enthesitis from abnormalities in five lower limb sites, and the MASEI (Madrid Sonography Enthesitis Index), which additionally includes calcifications and Doppler signals as elemental lesions as well as abnormalities of the olecranon tuberosity enthesis.

The average ages were 52, 53, and 42 years in the psoriasis, psoriatic arthritis, and healthy volunteer groups, respectively, and men accounted for 64%, 57%, and 32% of participants. Corresponding mean body mass indices were 27, 30, and 26 kg/m², respectively.

In all, 12 anatomical sites were assessed. The mean number showing ultrasonographic enthesitis differed significantly across groups, reported study coauthor Jai P. Jayakar at the annual meeting of the Canadian Rheumatology Association. The number of anatomical sites that showed enthesitis was highest in the psoriatic arthritis group (7.1), intermediate in the psoriasis group (5), and lowest in healthy volunteers (4).

There was also a significant, graded difference across groups in GUESS scores (8.9, 5.6, and 4.4 out of a possible 36, respectively, for psoriatic arthritis, psoriasis, and healthy controls) and in MASEI scores (18.5, 9.9, and 7.7 respectively for psoriatic arthritis, psoriasis, and healthy controls out of a possible 136). However, in multivariate analyses, disease status was not associated with these scores; only increasing age and BMI showed significant associations.

"Our study is one of the first comparative assessments of subclinical enthesitis in psoriasis vs. psoriatic arthritis," noted Mr. Jayakar. "Our results reveal that the prevalence of ultrasonographic entheseal abnormalities and indices of entheseal burden ... are greater in psoriatic arthritis than in psoriasis; however, this relationship may be modulated in a multifactorial manner by factors other than disease status, such as age and body mass index.

"Now, it is possible that enthesitis could be of predictive value in specific patient subgroups – for example, age- or obesity-stratified subgroups," he added. "However, larger studies are needed to confirm the utility of subclinical enthesitis as a predictive factor for the development of psoriatic arthritis in patients with psoriasis."

How could the investigators be certain, a session attendee asked, that they were detecting disease-related enthesitis and not simply mechanical tendonitis?

That is a valid concern, given the lack of consensus among rheumatologists as to which ultrasonographic abnormalities result from degeneration, inflammation, mechanical stress, or other etiologies, acknowledged Mr. Jayakar, a medical student at the University of Western Ontario, London. Large cohorts with well-defined disease status would be required to investigate this further, he said.

"One direction in which we could move forward is if we can find specific elemental lesions – or aggregates of elemental lesions – that are of predictive value, then perhaps those could be used pragmatically to help us in our clinical management," he noted. "But as of now, the pathophysiological underpinnings of these abnormalities are not very well described."

Mr. Jayakar disclosed no relevant conflicts of interest.

VICTORIA, B.C. – Subclinical enthesitis occurs more commonly in patients with psoriatic arthritis than in those with psoriasis, possibly as a result of age and obesity rather than disease severity, to judge from the findings of a cross-sectional study conducted by investigators at Toronto Western Hospital.

The investigators used ultrasound as well as clinical examination to assess the extent, if any, of enthesitis in study participants, who were 59 patients with psoriatic arthritis and 79 patients with psoriasis. Study participants were recruited from longitudinal cohorts. The control group was made up of 60 healthy volunteers who did not have any personal or family history of spondyloarthropathy. They were evaluated for enthesitis at sites in the calcaneus, knee, and olecranon.

Findings on ultrasound – any enthesophytes, bony erosions, tendon thickness, and bursitis, within tendons – were scored using GUESS (Glasgow Ultrasound Enthesitis Scoring System), which reflects the overall burden bilaterally of enthesitis from abnormalities in five lower limb sites, and the MASEI (Madrid Sonography Enthesitis Index), which additionally includes calcifications and Doppler signals as elemental lesions as well as abnormalities of the olecranon tuberosity enthesis.

The average ages were 52, 53, and 42 years in the psoriasis, psoriatic arthritis, and healthy volunteer groups, respectively, and men accounted for 64%, 57%, and 32% of participants. Corresponding mean body mass indices were 27, 30, and 26 kg/m², respectively.

In all, 12 anatomical sites were assessed. The mean number showing ultrasonographic enthesitis differed significantly across groups, reported study coauthor Jai P. Jayakar at the annual meeting of the Canadian Rheumatology Association. The number of anatomical sites that showed enthesitis was highest in the psoriatic arthritis group (7.1), intermediate in the psoriasis group (5), and lowest in healthy volunteers (4).

There was also a significant, graded difference across groups in GUESS scores (8.9, 5.6, and 4.4 out of a possible 36, respectively, for psoriatic arthritis, psoriasis, and healthy controls) and in MASEI scores (18.5, 9.9, and 7.7 respectively for psoriatic arthritis, psoriasis, and healthy controls out of a possible 136). However, in multivariate analyses, disease status was not associated with these scores; only increasing age and BMI showed significant associations.

"Our study is one of the first comparative assessments of subclinical enthesitis in psoriasis vs. psoriatic arthritis," noted Mr. Jayakar. "Our results reveal that the prevalence of ultrasonographic entheseal abnormalities and indices of entheseal burden ... are greater in psoriatic arthritis than in psoriasis; however, this relationship may be modulated in a multifactorial manner by factors other than disease status, such as age and body mass index.

"Now, it is possible that enthesitis could be of predictive value in specific patient subgroups – for example, age- or obesity-stratified subgroups," he added. "However, larger studies are needed to confirm the utility of subclinical enthesitis as a predictive factor for the development of psoriatic arthritis in patients with psoriasis."

How could the investigators be certain, a session attendee asked, that they were detecting disease-related enthesitis and not simply mechanical tendonitis?

That is a valid concern, given the lack of consensus among rheumatologists as to which ultrasonographic abnormalities result from degeneration, inflammation, mechanical stress, or other etiologies, acknowledged Mr. Jayakar, a medical student at the University of Western Ontario, London. Large cohorts with well-defined disease status would be required to investigate this further, he said.

"One direction in which we could move forward is if we can find specific elemental lesions – or aggregates of elemental lesions – that are of predictive value, then perhaps those could be used pragmatically to help us in our clinical management," he noted. "But as of now, the pathophysiological underpinnings of these abnormalities are not very well described."

Mr. Jayakar disclosed no relevant conflicts of interest.

VICTORIA, B.C. – Subclinical enthesitis occurs more commonly in patients with psoriatic arthritis than in those with psoriasis, possibly as a result of age and obesity rather than disease severity, to judge from the findings of a cross-sectional study conducted by investigators at Toronto Western Hospital.

The investigators used ultrasound as well as clinical examination to assess the extent, if any, of enthesitis in study participants, who were 59 patients with psoriatic arthritis and 79 patients with psoriasis. Study participants were recruited from longitudinal cohorts. The control group was made up of 60 healthy volunteers who did not have any personal or family history of spondyloarthropathy. They were evaluated for enthesitis at sites in the calcaneus, knee, and olecranon.

Findings on ultrasound – any enthesophytes, bony erosions, tendon thickness, and bursitis, within tendons – were scored using GUESS (Glasgow Ultrasound Enthesitis Scoring System), which reflects the overall burden bilaterally of enthesitis from abnormalities in five lower limb sites, and the MASEI (Madrid Sonography Enthesitis Index), which additionally includes calcifications and Doppler signals as elemental lesions as well as abnormalities of the olecranon tuberosity enthesis.

The average ages were 52, 53, and 42 years in the psoriasis, psoriatic arthritis, and healthy volunteer groups, respectively, and men accounted for 64%, 57%, and 32% of participants. Corresponding mean body mass indices were 27, 30, and 26 kg/m², respectively.

In all, 12 anatomical sites were assessed. The mean number showing ultrasonographic enthesitis differed significantly across groups, reported study coauthor Jai P. Jayakar at the annual meeting of the Canadian Rheumatology Association. The number of anatomical sites that showed enthesitis was highest in the psoriatic arthritis group (7.1), intermediate in the psoriasis group (5), and lowest in healthy volunteers (4).

There was also a significant, graded difference across groups in GUESS scores (8.9, 5.6, and 4.4 out of a possible 36, respectively, for psoriatic arthritis, psoriasis, and healthy controls) and in MASEI scores (18.5, 9.9, and 7.7 respectively for psoriatic arthritis, psoriasis, and healthy controls out of a possible 136). However, in multivariate analyses, disease status was not associated with these scores; only increasing age and BMI showed significant associations.

"Our study is one of the first comparative assessments of subclinical enthesitis in psoriasis vs. psoriatic arthritis," noted Mr. Jayakar. "Our results reveal that the prevalence of ultrasonographic entheseal abnormalities and indices of entheseal burden ... are greater in psoriatic arthritis than in psoriasis; however, this relationship may be modulated in a multifactorial manner by factors other than disease status, such as age and body mass index.

"Now, it is possible that enthesitis could be of predictive value in specific patient subgroups – for example, age- or obesity-stratified subgroups," he added. "However, larger studies are needed to confirm the utility of subclinical enthesitis as a predictive factor for the development of psoriatic arthritis in patients with psoriasis."

How could the investigators be certain, a session attendee asked, that they were detecting disease-related enthesitis and not simply mechanical tendonitis?

That is a valid concern, given the lack of consensus among rheumatologists as to which ultrasonographic abnormalities result from degeneration, inflammation, mechanical stress, or other etiologies, acknowledged Mr. Jayakar, a medical student at the University of Western Ontario, London. Large cohorts with well-defined disease status would be required to investigate this further, he said.

"One direction in which we could move forward is if we can find specific elemental lesions – or aggregates of elemental lesions – that are of predictive value, then perhaps those could be used pragmatically to help us in our clinical management," he noted. "But as of now, the pathophysiological underpinnings of these abnormalities are not very well described."

Mr. Jayakar disclosed no relevant conflicts of interest.

Outcomes of pregnancy in women with systemic lupus erythematosus have improved over the past 50 years, with dramatic reductions in rates of pregnancy loss and preterm delivery. These gains are due in large part to better management of lupus before and during pregnancy, a challenge that requires applying both evidence and clinical judgment on a case-by-case basis.

Prepregnancy Evaluation

All women with lupus should have a rheumatologic evaluation before conceiving to assess the likely safety of pregnancy. This evaluation includes clinical assessment with consideration of factors such as minor and major organ manifestations, comorbidities, medications, time since last flare, and current health.

It also includes careful assessment of renal status and updating of routine lab work. Serology should include testing for anti-Ro and anti-La antibodies, and for antiphospholipid antibodies – both lupus anticoagulant and anticardiolipin antibodies. Accumulating data suggest that lupus anticoagulant is by far the more important antiphospholipid antibody.

The presence of anti-Ro and/or anti-La antibodies always changes pregnancy management, prompting fetal echocardiographic monitoring because of the potential for congenital heart block. In contrast, the presence of antiphospholipid antibodies typically warrants aspirin therapy only if a woman has had clinical manifestations; otherwise, it may just be an antibody looking for a problem.

The medications assessed include any taken to treat lupus and any taken to manage complications of the disease, such as calcium channel blockers and angiotensin-converting enzyme inhibitors. Some medications may require discontinuation, depending on their teratogenicity profile.

Fortunately, most of the mainstay drugs used to treat lupus are safe in pregnancy. For example, prednisone can be continued, although women must be counseled about the small increased risk to the fetus of cleft lip and palate that may be related to dose. Similarly, hydroxychloroquine (Plaquenil) has a great safety track record in pregnancy and should be left in place. The risk of a flare when these drugs are stopped is far greater than any risk of toxicity.

Ideally, patients with lupus should be stable for at least 6 months on minimal medication before conceiving. The main risk factors for poor outcomes in women considering pregnancy are active disease, proteinuria exceeding 0.5 g/day, hypertension, thrombocytopenia, antiphospholipid antibodies, and certain medications.

Impact of Renal Disease

Any major organ involvement in lupus is a concern during pregnancy, but renal disease is the most common and is also a strong prognostic indicator.

Proteinuria before pregnancy is worrisome because it will almost certainly worsen in the first trimester. Women who conceive with proteinuria of 2 g/day or higher often develop a preeclampsia-like condition that can rapidly lead not only to fetal death, but also to maternal death. This is a group who should avoid pregnancy.

Another group we worry about are women who have needed dialysis and have been able to stop, but still have an elevated serum creatinine level (150-200 micromol/L). We know that their creatinine will worsen considerably during pregnancy. Such patients are good candidates for in vitro fertilization with use of a gestational carrier.

On the other hand, women who have undergone kidney transplantation and have good renal function and are doing well otherwise can usually safely undertake pregnancy. Most antirejection drugs can be continued during the pregnancy, but mycophenolate mofetil (CellCept) is a notable exception.

Communication and Counseling

A critical aspect of caring for women of childbearing age who have lupus is maintaining a good open line of communication. Patients who think that their rheumatologist will discourage pregnancy often proceed anyway and may conceal information, sometimes with bad consequences. By seeing patients regularly and keeping communication channels open, you minimize the risk of women conceiving nonelectively or before they are healthy enough, and outcomes are better.

Two counseling strategies may be helpful here. The first is use of a simple traffic light metaphor in describing the likely safety of pregnancy. A green light means there is no reason why a woman can’t go through a pregnancy. A yellow light means that you have concerns but are going to work with her to achieve the best possible outcome; this is by far the most difficult area, and you have to decide whether you are comfortable dealing with it. A red light means the woman is not ready to conceive, and if she is pregnant, she should be counseled about termination.

The second strategy is use of a "light at the end of the tunnel" approach. With this approach, you work and bargain with the patient over time with the goal of eventually improving her health status to the point at which she can safely undertake pregnancy. This strategy requires you to maintain continued follow-up to ensure that the patient perceives that you are working with her to reach a stage where it is safe to undertake a pregnancy.

Fertility Treatment

When women with lupus undergo fertility treatment, rheumatologists should work closely with the reproductive endocrinology and infertility (REI) specialist to ensure the best possible outcomes. The rheumatologist must monitor the medical condition in women undergoing assisted reproductive technologies.

Rheumatologists should also have some basic familiarity with the medications used in fertility treatment as they can affect lupus activity. In particular, drug-induced estrogen levels during this treatment can be up to 20 times higher than those seen in a normal menstrual cycle, and hyperestrogenemia may precipitate a flare in some women.

It is not yet clear whether drugs that produce elevation of endogenous estrogen levels, such as clomiphene citrate (Clomid), have the same effect as drugs that deliver a large amount of synthetic, exogenous estrogen, such as the combined oral contraceptive.

Management in Pregnancy

When managing lupus during pregnancy, remember that it is a two-way street: The disease may affect the pregnancy, and the pregnancy may affect the disease. Of all the diseases out there, lupus is the perfect example of this phenomenon.

Rheumatologic assessments during pregnancy entail monitoring disease activity with vigilance for problems and awareness of special issues posed by pregnancy, such as hypercoagulability. Clinical course can be difficult to predict as the sensitivity of lupus to the hormonal changes of pregnancy varies on a case-by-case basis.

Pregnant patients with lupus are typically seen by a rheumatologist every 1-8 weeks depending on disease activity and other issues. Routine lab work is generally repeated roughly every 4 weeks, unless circumstances require more frequent monitoring, but serology does not have to be done that often.

Certain factors present in the first trimester are associated with a poor prognosis and may warrant discussion of termination. They include active disease, hypertension, proteinuria of at least 2 g/day, and an increased serum creatinine level.

If patients have ever had renal impairment from their lupus, no matter how stable they are going into the pregnancy, you are likely to see elevated protein excretion between 20 and 25 weeks. This is caused by the increased glomerular permeability that occurs in pregnancy, and patients can develop significant proteinuria.

Although management in the lupus patient during pregnancy is a multidisciplinary team effort, it is wise to have a lead internist coordinating all of the patient’s care. Often, pregnancies in this population result in involvement of many subspecialists, sometimes to the detriment of good communication.

Dr. Laskin disclosed that he has affiliations with Amgen, GlaxoSmithKline, Janssen Pharmaceutical, and UCB Pharma.

Dr. Laskin is founding director of the Obstetric Medicine Program at the University of Toronto and a founding partner of the LifeQuest Centre for Reproductive Medicine, also in Toronto.

Outcomes of pregnancy in women with systemic lupus erythematosus have improved over the past 50 years, with dramatic reductions in rates of pregnancy loss and preterm delivery. These gains are due in large part to better management of lupus before and during pregnancy, a challenge that requires applying both evidence and clinical judgment on a case-by-case basis.

Prepregnancy Evaluation

All women with lupus should have a rheumatologic evaluation before conceiving to assess the likely safety of pregnancy. This evaluation includes clinical assessment with consideration of factors such as minor and major organ manifestations, comorbidities, medications, time since last flare, and current health.

It also includes careful assessment of renal status and updating of routine lab work. Serology should include testing for anti-Ro and anti-La antibodies, and for antiphospholipid antibodies – both lupus anticoagulant and anticardiolipin antibodies. Accumulating data suggest that lupus anticoagulant is by far the more important antiphospholipid antibody.

The presence of anti-Ro and/or anti-La antibodies always changes pregnancy management, prompting fetal echocardiographic monitoring because of the potential for congenital heart block. In contrast, the presence of antiphospholipid antibodies typically warrants aspirin therapy only if a woman has had clinical manifestations; otherwise, it may just be an antibody looking for a problem.

The medications assessed include any taken to treat lupus and any taken to manage complications of the disease, such as calcium channel blockers and angiotensin-converting enzyme inhibitors. Some medications may require discontinuation, depending on their teratogenicity profile.

Fortunately, most of the mainstay drugs used to treat lupus are safe in pregnancy. For example, prednisone can be continued, although women must be counseled about the small increased risk to the fetus of cleft lip and palate that may be related to dose. Similarly, hydroxychloroquine (Plaquenil) has a great safety track record in pregnancy and should be left in place. The risk of a flare when these drugs are stopped is far greater than any risk of toxicity.

Ideally, patients with lupus should be stable for at least 6 months on minimal medication before conceiving. The main risk factors for poor outcomes in women considering pregnancy are active disease, proteinuria exceeding 0.5 g/day, hypertension, thrombocytopenia, antiphospholipid antibodies, and certain medications.

Impact of Renal Disease

Any major organ involvement in lupus is a concern during pregnancy, but renal disease is the most common and is also a strong prognostic indicator.

Proteinuria before pregnancy is worrisome because it will almost certainly worsen in the first trimester. Women who conceive with proteinuria of 2 g/day or higher often develop a preeclampsia-like condition that can rapidly lead not only to fetal death, but also to maternal death. This is a group who should avoid pregnancy.

Another group we worry about are women who have needed dialysis and have been able to stop, but still have an elevated serum creatinine level (150-200 micromol/L). We know that their creatinine will worsen considerably during pregnancy. Such patients are good candidates for in vitro fertilization with use of a gestational carrier.

On the other hand, women who have undergone kidney transplantation and have good renal function and are doing well otherwise can usually safely undertake pregnancy. Most antirejection drugs can be continued during the pregnancy, but mycophenolate mofetil (CellCept) is a notable exception.

Communication and Counseling

A critical aspect of caring for women of childbearing age who have lupus is maintaining a good open line of communication. Patients who think that their rheumatologist will discourage pregnancy often proceed anyway and may conceal information, sometimes with bad consequences. By seeing patients regularly and keeping communication channels open, you minimize the risk of women conceiving nonelectively or before they are healthy enough, and outcomes are better.

Two counseling strategies may be helpful here. The first is use of a simple traffic light metaphor in describing the likely safety of pregnancy. A green light means there is no reason why a woman can’t go through a pregnancy. A yellow light means that you have concerns but are going to work with her to achieve the best possible outcome; this is by far the most difficult area, and you have to decide whether you are comfortable dealing with it. A red light means the woman is not ready to conceive, and if she is pregnant, she should be counseled about termination.

The second strategy is use of a "light at the end of the tunnel" approach. With this approach, you work and bargain with the patient over time with the goal of eventually improving her health status to the point at which she can safely undertake pregnancy. This strategy requires you to maintain continued follow-up to ensure that the patient perceives that you are working with her to reach a stage where it is safe to undertake a pregnancy.

Fertility Treatment

When women with lupus undergo fertility treatment, rheumatologists should work closely with the reproductive endocrinology and infertility (REI) specialist to ensure the best possible outcomes. The rheumatologist must monitor the medical condition in women undergoing assisted reproductive technologies.

Rheumatologists should also have some basic familiarity with the medications used in fertility treatment as they can affect lupus activity. In particular, drug-induced estrogen levels during this treatment can be up to 20 times higher than those seen in a normal menstrual cycle, and hyperestrogenemia may precipitate a flare in some women.

It is not yet clear whether drugs that produce elevation of endogenous estrogen levels, such as clomiphene citrate (Clomid), have the same effect as drugs that deliver a large amount of synthetic, exogenous estrogen, such as the combined oral contraceptive.

Management in Pregnancy

When managing lupus during pregnancy, remember that it is a two-way street: The disease may affect the pregnancy, and the pregnancy may affect the disease. Of all the diseases out there, lupus is the perfect example of this phenomenon.

Rheumatologic assessments during pregnancy entail monitoring disease activity with vigilance for problems and awareness of special issues posed by pregnancy, such as hypercoagulability. Clinical course can be difficult to predict as the sensitivity of lupus to the hormonal changes of pregnancy varies on a case-by-case basis.

Pregnant patients with lupus are typically seen by a rheumatologist every 1-8 weeks depending on disease activity and other issues. Routine lab work is generally repeated roughly every 4 weeks, unless circumstances require more frequent monitoring, but serology does not have to be done that often.

Certain factors present in the first trimester are associated with a poor prognosis and may warrant discussion of termination. They include active disease, hypertension, proteinuria of at least 2 g/day, and an increased serum creatinine level.

If patients have ever had renal impairment from their lupus, no matter how stable they are going into the pregnancy, you are likely to see elevated protein excretion between 20 and 25 weeks. This is caused by the increased glomerular permeability that occurs in pregnancy, and patients can develop significant proteinuria.

Although management in the lupus patient during pregnancy is a multidisciplinary team effort, it is wise to have a lead internist coordinating all of the patient’s care. Often, pregnancies in this population result in involvement of many subspecialists, sometimes to the detriment of good communication.

Dr. Laskin disclosed that he has affiliations with Amgen, GlaxoSmithKline, Janssen Pharmaceutical, and UCB Pharma.

Dr. Laskin is founding director of the Obstetric Medicine Program at the University of Toronto and a founding partner of the LifeQuest Centre for Reproductive Medicine, also in Toronto.

Outcomes of pregnancy in women with systemic lupus erythematosus have improved over the past 50 years, with dramatic reductions in rates of pregnancy loss and preterm delivery. These gains are due in large part to better management of lupus before and during pregnancy, a challenge that requires applying both evidence and clinical judgment on a case-by-case basis.

Prepregnancy Evaluation

All women with lupus should have a rheumatologic evaluation before conceiving to assess the likely safety of pregnancy. This evaluation includes clinical assessment with consideration of factors such as minor and major organ manifestations, comorbidities, medications, time since last flare, and current health.

It also includes careful assessment of renal status and updating of routine lab work. Serology should include testing for anti-Ro and anti-La antibodies, and for antiphospholipid antibodies – both lupus anticoagulant and anticardiolipin antibodies. Accumulating data suggest that lupus anticoagulant is by far the more important antiphospholipid antibody.

The presence of anti-Ro and/or anti-La antibodies always changes pregnancy management, prompting fetal echocardiographic monitoring because of the potential for congenital heart block. In contrast, the presence of antiphospholipid antibodies typically warrants aspirin therapy only if a woman has had clinical manifestations; otherwise, it may just be an antibody looking for a problem.

The medications assessed include any taken to treat lupus and any taken to manage complications of the disease, such as calcium channel blockers and angiotensin-converting enzyme inhibitors. Some medications may require discontinuation, depending on their teratogenicity profile.

Fortunately, most of the mainstay drugs used to treat lupus are safe in pregnancy. For example, prednisone can be continued, although women must be counseled about the small increased risk to the fetus of cleft lip and palate that may be related to dose. Similarly, hydroxychloroquine (Plaquenil) has a great safety track record in pregnancy and should be left in place. The risk of a flare when these drugs are stopped is far greater than any risk of toxicity.

Ideally, patients with lupus should be stable for at least 6 months on minimal medication before conceiving. The main risk factors for poor outcomes in women considering pregnancy are active disease, proteinuria exceeding 0.5 g/day, hypertension, thrombocytopenia, antiphospholipid antibodies, and certain medications.

Impact of Renal Disease

Any major organ involvement in lupus is a concern during pregnancy, but renal disease is the most common and is also a strong prognostic indicator.

Proteinuria before pregnancy is worrisome because it will almost certainly worsen in the first trimester. Women who conceive with proteinuria of 2 g/day or higher often develop a preeclampsia-like condition that can rapidly lead not only to fetal death, but also to maternal death. This is a group who should avoid pregnancy.

Another group we worry about are women who have needed dialysis and have been able to stop, but still have an elevated serum creatinine level (150-200 micromol/L). We know that their creatinine will worsen considerably during pregnancy. Such patients are good candidates for in vitro fertilization with use of a gestational carrier.

On the other hand, women who have undergone kidney transplantation and have good renal function and are doing well otherwise can usually safely undertake pregnancy. Most antirejection drugs can be continued during the pregnancy, but mycophenolate mofetil (CellCept) is a notable exception.

Communication and Counseling

A critical aspect of caring for women of childbearing age who have lupus is maintaining a good open line of communication. Patients who think that their rheumatologist will discourage pregnancy often proceed anyway and may conceal information, sometimes with bad consequences. By seeing patients regularly and keeping communication channels open, you minimize the risk of women conceiving nonelectively or before they are healthy enough, and outcomes are better.

Two counseling strategies may be helpful here. The first is use of a simple traffic light metaphor in describing the likely safety of pregnancy. A green light means there is no reason why a woman can’t go through a pregnancy. A yellow light means that you have concerns but are going to work with her to achieve the best possible outcome; this is by far the most difficult area, and you have to decide whether you are comfortable dealing with it. A red light means the woman is not ready to conceive, and if she is pregnant, she should be counseled about termination.

The second strategy is use of a "light at the end of the tunnel" approach. With this approach, you work and bargain with the patient over time with the goal of eventually improving her health status to the point at which she can safely undertake pregnancy. This strategy requires you to maintain continued follow-up to ensure that the patient perceives that you are working with her to reach a stage where it is safe to undertake a pregnancy.

Fertility Treatment

When women with lupus undergo fertility treatment, rheumatologists should work closely with the reproductive endocrinology and infertility (REI) specialist to ensure the best possible outcomes. The rheumatologist must monitor the medical condition in women undergoing assisted reproductive technologies.

Rheumatologists should also have some basic familiarity with the medications used in fertility treatment as they can affect lupus activity. In particular, drug-induced estrogen levels during this treatment can be up to 20 times higher than those seen in a normal menstrual cycle, and hyperestrogenemia may precipitate a flare in some women.

It is not yet clear whether drugs that produce elevation of endogenous estrogen levels, such as clomiphene citrate (Clomid), have the same effect as drugs that deliver a large amount of synthetic, exogenous estrogen, such as the combined oral contraceptive.

Management in Pregnancy

When managing lupus during pregnancy, remember that it is a two-way street: The disease may affect the pregnancy, and the pregnancy may affect the disease. Of all the diseases out there, lupus is the perfect example of this phenomenon.

Rheumatologic assessments during pregnancy entail monitoring disease activity with vigilance for problems and awareness of special issues posed by pregnancy, such as hypercoagulability. Clinical course can be difficult to predict as the sensitivity of lupus to the hormonal changes of pregnancy varies on a case-by-case basis.

Pregnant patients with lupus are typically seen by a rheumatologist every 1-8 weeks depending on disease activity and other issues. Routine lab work is generally repeated roughly every 4 weeks, unless circumstances require more frequent monitoring, but serology does not have to be done that often.

Certain factors present in the first trimester are associated with a poor prognosis and may warrant discussion of termination. They include active disease, hypertension, proteinuria of at least 2 g/day, and an increased serum creatinine level.

If patients have ever had renal impairment from their lupus, no matter how stable they are going into the pregnancy, you are likely to see elevated protein excretion between 20 and 25 weeks. This is caused by the increased glomerular permeability that occurs in pregnancy, and patients can develop significant proteinuria.

Although management in the lupus patient during pregnancy is a multidisciplinary team effort, it is wise to have a lead internist coordinating all of the patient’s care. Often, pregnancies in this population result in involvement of many subspecialists, sometimes to the detriment of good communication.

Dr. Laskin disclosed that he has affiliations with Amgen, GlaxoSmithKline, Janssen Pharmaceutical, and UCB Pharma.

Dr. Laskin is founding director of the Obstetric Medicine Program at the University of Toronto and a founding partner of the LifeQuest Centre for Reproductive Medicine, also in Toronto.

VICTORIA, B.C. – Physician and patient assessments of disease activity in rheumatoid arthritis show considerable disagreement that seems to be driven by subjective perceptions of pain, a study has shown.

The study involved nearly 900 patients with early rheumatoid arthritis (RA) and 100 patients with established RA in remission, all of whom had been treated only with disease-modifying antirheumatic drugs (DMARDs). Findings on physician and patient assessments of disease activity disagreed to a clinically meaningful extent roughly one-fourth to one-third of the time, based on the results of this as-yet unpublished study, reported at the annual meeting of the Canadian Rheumatology Association.

In most cases of discordance, patients rated their RA as being worse than their physicians did. Findings from additional analyses suggested that the discrepancy was largely due to subjective pain, and pain levels showed some association with cumulative RA-related joint damage.

"For a rheumatologist who is using these global assessment scores" – the patient global assessment (PtGA) and the physician global assessment (MDGA) – "75% of the time, you can expect the patient to agree with you on their disease activity level. They are going to report a pretty similar score. But for the other 25% of the time, the patient’s going to say, ‘My disease is worse than what you think it is,’ " explained presenting author May Choi, a second-year medical student at the University of Alberta, Edmonton.

"We think it’s more a reflection of their subjective pain, and that pain is probably not in their joints – it probably has something to do with soft tissue pain, like fibromyalgia," she added. In patients with established disease, the pain appears to reflect "all of the joint damage they have accumulated over the years because of the RA. So it’s not a reflection of their current disease activity, but the damage that has resulted."

Physicians who find a discrepancy between assessments for a given patient should take a closer look to determine the reason, especially as it has implications for treatment, Ms. Choi advised in an interview. "If a patient is in a lot of pain, but a physician is feeling their joints and they don’t really see [an explanation for] what’s going on, they are not going to give them a drug for their joints. They are going to look at other reasons and treat them for that – pain that’s related to their soft tissues," she explained.

The study’s findings also suggest that the two assessments are complementary, and both should be used, she maintained. "I don’t think one is more important than the other. They provide different information" and in clinical studies, "absolutely, they should get both numbers to get the big picture."

Previous research has found a difference between physician and patient global assessments of RA disease activity, but the reason remains unknown, according to Ms. Choi. "This is an important question because physicians use this tool to monitor their patients, and we think it’s important to increase awareness that there is a difference. We wanted to look at reasons why this difference exists and what are its implications for patient management," she said.

For the study, which was supported by the Canadian Rheumatology Association–Roche Summer Studentship, the researchers identified 897 patients with early RA (mean disease duration, 0.5 years) from the Canadian Early Arthritis Cohort database and 100 patients with established RA in remission from one practice (mean disease duration, 18 years).

Scores were compared from the patient-completed PtGA and physician-completed MDGA. Discrepancy between results on the two 100-mm scales was assessed by subtracting the latter from the former and was classified as clinically meaningful if it was at least 30 mm.

Study results, reported in a poster session, revealed that in the early RA group, the PtGA and MDGA scores showed no discrepancy in 64% of patients. But in 24%, patients reported worse disease than their physicians did, and in 12%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting disease activity had lower swollen and tender joint counts and similar C-reactive protein levels. Yet they also reported more pain. "So here is a group of patients who are reporting a lot of pain, but it’s not in their joints necessarily," commented Ms. Choi. On the other hand, compared with their counterparts having no discrepancy, patients underreporting disease activity had higher swollen joint counts and C-reactive protein levels, and yet less pain. This finding may be related to differing pain thresholds across individuals, she noted, saying, "There are some patients like that. They are just not as sensitive."

In the established RA group, the PtGA and MDGA scores showed no discrepancy in 75% of patients. But in 24%, patients reported worse disease than their physicians did, and in 1%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting or under-reporting disease activity were younger; had a higher damaged joint count, erythrocyte sedimentation rate, and C-reactive protein level; and reported more pain.

"So in both groups, pain is a common theme," Ms. Choi pointed out. And indeed, additional analysis showed that reported pain scores were positively correlated with the magnitude of the PtGA-MDGA discrepancy (r = 0.84). Also, among the patients with established disease, pain scores were positively correlated with the number of damaged joints (rS = 0.37).

Ms. Choi said she had no relevant financial disclosures.

VICTORIA, B.C. – Physician and patient assessments of disease activity in rheumatoid arthritis show considerable disagreement that seems to be driven by subjective perceptions of pain, a study has shown.

The study involved nearly 900 patients with early rheumatoid arthritis (RA) and 100 patients with established RA in remission, all of whom had been treated only with disease-modifying antirheumatic drugs (DMARDs). Findings on physician and patient assessments of disease activity disagreed to a clinically meaningful extent roughly one-fourth to one-third of the time, based on the results of this as-yet unpublished study, reported at the annual meeting of the Canadian Rheumatology Association.

In most cases of discordance, patients rated their RA as being worse than their physicians did. Findings from additional analyses suggested that the discrepancy was largely due to subjective pain, and pain levels showed some association with cumulative RA-related joint damage.

"For a rheumatologist who is using these global assessment scores" – the patient global assessment (PtGA) and the physician global assessment (MDGA) – "75% of the time, you can expect the patient to agree with you on their disease activity level. They are going to report a pretty similar score. But for the other 25% of the time, the patient’s going to say, ‘My disease is worse than what you think it is,’ " explained presenting author May Choi, a second-year medical student at the University of Alberta, Edmonton.

"We think it’s more a reflection of their subjective pain, and that pain is probably not in their joints – it probably has something to do with soft tissue pain, like fibromyalgia," she added. In patients with established disease, the pain appears to reflect "all of the joint damage they have accumulated over the years because of the RA. So it’s not a reflection of their current disease activity, but the damage that has resulted."

Physicians who find a discrepancy between assessments for a given patient should take a closer look to determine the reason, especially as it has implications for treatment, Ms. Choi advised in an interview. "If a patient is in a lot of pain, but a physician is feeling their joints and they don’t really see [an explanation for] what’s going on, they are not going to give them a drug for their joints. They are going to look at other reasons and treat them for that – pain that’s related to their soft tissues," she explained.

The study’s findings also suggest that the two assessments are complementary, and both should be used, she maintained. "I don’t think one is more important than the other. They provide different information" and in clinical studies, "absolutely, they should get both numbers to get the big picture."

Previous research has found a difference between physician and patient global assessments of RA disease activity, but the reason remains unknown, according to Ms. Choi. "This is an important question because physicians use this tool to monitor their patients, and we think it’s important to increase awareness that there is a difference. We wanted to look at reasons why this difference exists and what are its implications for patient management," she said.

For the study, which was supported by the Canadian Rheumatology Association–Roche Summer Studentship, the researchers identified 897 patients with early RA (mean disease duration, 0.5 years) from the Canadian Early Arthritis Cohort database and 100 patients with established RA in remission from one practice (mean disease duration, 18 years).

Scores were compared from the patient-completed PtGA and physician-completed MDGA. Discrepancy between results on the two 100-mm scales was assessed by subtracting the latter from the former and was classified as clinically meaningful if it was at least 30 mm.

Study results, reported in a poster session, revealed that in the early RA group, the PtGA and MDGA scores showed no discrepancy in 64% of patients. But in 24%, patients reported worse disease than their physicians did, and in 12%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting disease activity had lower swollen and tender joint counts and similar C-reactive protein levels. Yet they also reported more pain. "So here is a group of patients who are reporting a lot of pain, but it’s not in their joints necessarily," commented Ms. Choi. On the other hand, compared with their counterparts having no discrepancy, patients underreporting disease activity had higher swollen joint counts and C-reactive protein levels, and yet less pain. This finding may be related to differing pain thresholds across individuals, she noted, saying, "There are some patients like that. They are just not as sensitive."

In the established RA group, the PtGA and MDGA scores showed no discrepancy in 75% of patients. But in 24%, patients reported worse disease than their physicians did, and in 1%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting or under-reporting disease activity were younger; had a higher damaged joint count, erythrocyte sedimentation rate, and C-reactive protein level; and reported more pain.

"So in both groups, pain is a common theme," Ms. Choi pointed out. And indeed, additional analysis showed that reported pain scores were positively correlated with the magnitude of the PtGA-MDGA discrepancy (r = 0.84). Also, among the patients with established disease, pain scores were positively correlated with the number of damaged joints (rS = 0.37).

Ms. Choi said she had no relevant financial disclosures.

VICTORIA, B.C. – Physician and patient assessments of disease activity in rheumatoid arthritis show considerable disagreement that seems to be driven by subjective perceptions of pain, a study has shown.

The study involved nearly 900 patients with early rheumatoid arthritis (RA) and 100 patients with established RA in remission, all of whom had been treated only with disease-modifying antirheumatic drugs (DMARDs). Findings on physician and patient assessments of disease activity disagreed to a clinically meaningful extent roughly one-fourth to one-third of the time, based on the results of this as-yet unpublished study, reported at the annual meeting of the Canadian Rheumatology Association.

In most cases of discordance, patients rated their RA as being worse than their physicians did. Findings from additional analyses suggested that the discrepancy was largely due to subjective pain, and pain levels showed some association with cumulative RA-related joint damage.

"For a rheumatologist who is using these global assessment scores" – the patient global assessment (PtGA) and the physician global assessment (MDGA) – "75% of the time, you can expect the patient to agree with you on their disease activity level. They are going to report a pretty similar score. But for the other 25% of the time, the patient’s going to say, ‘My disease is worse than what you think it is,’ " explained presenting author May Choi, a second-year medical student at the University of Alberta, Edmonton.

"We think it’s more a reflection of their subjective pain, and that pain is probably not in their joints – it probably has something to do with soft tissue pain, like fibromyalgia," she added. In patients with established disease, the pain appears to reflect "all of the joint damage they have accumulated over the years because of the RA. So it’s not a reflection of their current disease activity, but the damage that has resulted."

Physicians who find a discrepancy between assessments for a given patient should take a closer look to determine the reason, especially as it has implications for treatment, Ms. Choi advised in an interview. "If a patient is in a lot of pain, but a physician is feeling their joints and they don’t really see [an explanation for] what’s going on, they are not going to give them a drug for their joints. They are going to look at other reasons and treat them for that – pain that’s related to their soft tissues," she explained.

The study’s findings also suggest that the two assessments are complementary, and both should be used, she maintained. "I don’t think one is more important than the other. They provide different information" and in clinical studies, "absolutely, they should get both numbers to get the big picture."

Previous research has found a difference between physician and patient global assessments of RA disease activity, but the reason remains unknown, according to Ms. Choi. "This is an important question because physicians use this tool to monitor their patients, and we think it’s important to increase awareness that there is a difference. We wanted to look at reasons why this difference exists and what are its implications for patient management," she said.

For the study, which was supported by the Canadian Rheumatology Association–Roche Summer Studentship, the researchers identified 897 patients with early RA (mean disease duration, 0.5 years) from the Canadian Early Arthritis Cohort database and 100 patients with established RA in remission from one practice (mean disease duration, 18 years).

Scores were compared from the patient-completed PtGA and physician-completed MDGA. Discrepancy between results on the two 100-mm scales was assessed by subtracting the latter from the former and was classified as clinically meaningful if it was at least 30 mm.

Study results, reported in a poster session, revealed that in the early RA group, the PtGA and MDGA scores showed no discrepancy in 64% of patients. But in 24%, patients reported worse disease than their physicians did, and in 12%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting disease activity had lower swollen and tender joint counts and similar C-reactive protein levels. Yet they also reported more pain. "So here is a group of patients who are reporting a lot of pain, but it’s not in their joints necessarily," commented Ms. Choi. On the other hand, compared with their counterparts having no discrepancy, patients underreporting disease activity had higher swollen joint counts and C-reactive protein levels, and yet less pain. This finding may be related to differing pain thresholds across individuals, she noted, saying, "There are some patients like that. They are just not as sensitive."

In the established RA group, the PtGA and MDGA scores showed no discrepancy in 75% of patients. But in 24%, patients reported worse disease than their physicians did, and in 1%, physicians reported worse disease than patients did.

Compared with their counterparts having no discrepancy, patients over-reporting or under-reporting disease activity were younger; had a higher damaged joint count, erythrocyte sedimentation rate, and C-reactive protein level; and reported more pain.

"So in both groups, pain is a common theme," Ms. Choi pointed out. And indeed, additional analysis showed that reported pain scores were positively correlated with the magnitude of the PtGA-MDGA discrepancy (r = 0.84). Also, among the patients with established disease, pain scores were positively correlated with the number of damaged joints (rS = 0.37).

Ms. Choi said she had no relevant financial disclosures.

POINT: All rheumatologists should offer it to their patients.

Like other point-of-care tests used all the time in medicine – spirometry, blood pressure measurement, the finger-stick glucose test – point-of-care ultrasound is invaluable in the diagnosis and management of rheumatologic conditions.

Ultrasound has a number of merits: It is portable and inexpensive; can be used on multiple joints; allows imaging of both bones and soft tissue, and assessment of vascularity; permits contralateral-side comparison; facilitates accurate injections; and serves as an informational and educational tool for patients. Contemporary machines have resolution down to 0.1 mm, much greater than the 1-2 mm for magnetic resonance imaging.

Photo: Susan London/IMNG Medical Media

A recent poll of Canadian rheumatologists about musculoskeletal ultrasound yielded some eye-opening findings. For example, 83% reported having to wait more than 2 weeks to obtain this exam if they referred patients to a radiology service, and just 56% reported that their radiology service offered assessment for inflammatory arthritis (Clin. Rheumatol. 2011;30:1277-83).

We know that information provided by ultrasound changes behavior in rheumatology: It leads to a change in diagnosis in 53% of patients and a change in management in 56% (Arthritis Rheum. 2001;44:2932-3). Ultrasound also improves diagnostic confidence in clinical findings (Skeletal Radiol. 2009;38:1049-54). Diagnostic certainty is key, as musculoskeletal symptoms are some of the most imprecise, and although we now have powerful medications for rheumatologic diseases, they don’t come cheap. Yet we are basing treatment decisions on clinical assessment alone. In an era of budget constraints, we owe it to patients and payers to make an accurate diagnosis and assessment: This is really all about providing an adequate standard of diagnosis and care.

In addition to aiding diagnosis, ultrasound helps in other ways, such as determining the risk of erosions (Arthritis Res. Ther. 2003;5:210-3) and predicting response to treatment (Arthritis Care Res. 2011;63:1477-81). It is more sensitive than clinical measures for assessing disease remission (Arthritis Rheum. 2008;58:2958-67). As patients have to live decades with their joints, and their quality of life is on the line, it is our responsibility to confirm clinically apparent remission with ultrasound.

An ultrasound exam can be done in the office in as few as 5 minutes; often, evaluation of just a single joint will suffice. The time spent more than makes up for the time that would be needed to coordinate a referral to radiology and to follow up on that referral. And there are plenty of examples on how to successfully integrate ultrasound into your office workflow.

In summary, ultrasound should be used as an extension of our clinical examination. It allows for immediate imaging correlation, and it assists with decision making in an environment where radiology services have limitations. It is also phenomenally powerful when it comes to patient contact and education. True point-of-care ultrasound is fast, high quality, and cost efficient. If you show this information to patients, their families, taxpayers, and politicians, they will agree: There is no question that point-of-care ultrasound is the way to go.

Dr. Maggie Larché is a rheumatologist at St. Joseph’s Hospital and McMaster University Hospital, both in Hamilton, Ont. She is also vice president and treasurer of the Canadian Rheumatology Ultrasound Society. Dr. JohannesRoth is head of pediatric rheumatology at Children’s Hospital of Eastern Ontario, Ottawa, and is president of the Canadian Rheumatology Ultrasound Society. Dr. Larché disclosed no relevant conflicts of interest. Dr. Roth disclosed no relevant conflicts of interest.

COUNTERPOINT: Its use at present is best left to experts.

Ultrasound is an amazing tool, and we are not disputing its merits. Thus, the question is not so much whether it should be used in the rheumatologist’s office, but whether you should use it in your office.

Europe is often cited as a hotbed of ultrasound use in rheumatology to be emulated. But in fact, in only 10% of European countries do the majority of rheumatologists use ultrasound, and in no country do the majority of rheumatologists perform ultrasound-guided arthrocentesis (Rheumatol. 2012;51:184-90).

We don’t know if it is feasible to use ultrasound findings as outcome measures in routine clinical care. A recent systematic review noted the difficulty of determining the minimum number of joints to be included in a global ultrasound score and recommended further validation (J. Rheumatol. 2011;38:2055-62). The time needed to perform the exam ranged from 15 to 60 minutes.

Indeed, time and resource constraints are rightly cited as major barriers to wider use of ultrasound in the rheumatology office. Exam time is not the only consideration: The time to acquire ultrasound skills and then to maintain and improve them is also considerable. There is unquestionably a learning curve; it takes about 4-6 months to become good at this. Then you have to continually upgrade your skills.

Our patients already wait for care. If we begin doing ultrasound in the office, they will wait even longer to see us. This is important, as, for example, just a few months of early rheumatoid arthritis is destructive to the joints. Additionally, even with rheumatologists working at their current pace, there is already a projected shortfall of nearly two-thirds in the number needed in Canada by 2026 (J. Rheumatol. 2010;37:1749-55).

Ultrasound-guided needle placement in joint spaces sounds wonderful, but we need more long-term proof that it improves outcomes. For instance, when it comes to sacroiliac joint injections, clinical outcome is the same whether the needle is placed in the joint space or in the adjacent tissue (Rheumatology 2010;49:1479-82).

Ultrasound is incredibly subjective and user dependent. You need a lot of training to become good at it: There is only fair to moderate agreement in assessing synovitis for beginners just getting up to speed (Int. J. Rheumatol. 2010;164518). So unless you are an elite expert, you are not going to be that proficient, and there is potential for doing more harm than good.

In summary, point-of-care ultrasound in rheumatology needs more investigation. At present, we recommend against widespread adoption in rheumatologists’ offices. Rheumatologists’ time is too precious to waste on ultrasound exams. Even cardiologists and obstetrician-gynecologists have techs who do the exams; if we try to do them ourselves, our patient wait lists will skyrocket. The cost to you and society makes the choice clear: We should not be doing ultrasound routinely in our office.

Dr. Christopher Penney is a rheumatologist at Foothills Hospital in Calgary, Alta. Dr. David Collins is a rheumatologist at Vancouver (B.C.) General Hospital. Dr. Penney disclosed no relevant conflicts of interest. Dr. Collins disclosed no relevant conflicts of interest. The comments were based on presentations given at the annual meeting of the Canadian Rheumatology Association in Victoria, B.C.

POINT: All rheumatologists should offer it to their patients.

Like other point-of-care tests used all the time in medicine – spirometry, blood pressure measurement, the finger-stick glucose test – point-of-care ultrasound is invaluable in the diagnosis and management of rheumatologic conditions.

Ultrasound has a number of merits: It is portable and inexpensive; can be used on multiple joints; allows imaging of both bones and soft tissue, and assessment of vascularity; permits contralateral-side comparison; facilitates accurate injections; and serves as an informational and educational tool for patients. Contemporary machines have resolution down to 0.1 mm, much greater than the 1-2 mm for magnetic resonance imaging.

Photo: Susan London/IMNG Medical Media

A recent poll of Canadian rheumatologists about musculoskeletal ultrasound yielded some eye-opening findings. For example, 83% reported having to wait more than 2 weeks to obtain this exam if they referred patients to a radiology service, and just 56% reported that their radiology service offered assessment for inflammatory arthritis (Clin. Rheumatol. 2011;30:1277-83).

We know that information provided by ultrasound changes behavior in rheumatology: It leads to a change in diagnosis in 53% of patients and a change in management in 56% (Arthritis Rheum. 2001;44:2932-3). Ultrasound also improves diagnostic confidence in clinical findings (Skeletal Radiol. 2009;38:1049-54). Diagnostic certainty is key, as musculoskeletal symptoms are some of the most imprecise, and although we now have powerful medications for rheumatologic diseases, they don’t come cheap. Yet we are basing treatment decisions on clinical assessment alone. In an era of budget constraints, we owe it to patients and payers to make an accurate diagnosis and assessment: This is really all about providing an adequate standard of diagnosis and care.

In addition to aiding diagnosis, ultrasound helps in other ways, such as determining the risk of erosions (Arthritis Res. Ther. 2003;5:210-3) and predicting response to treatment (Arthritis Care Res. 2011;63:1477-81). It is more sensitive than clinical measures for assessing disease remission (Arthritis Rheum. 2008;58:2958-67). As patients have to live decades with their joints, and their quality of life is on the line, it is our responsibility to confirm clinically apparent remission with ultrasound.

An ultrasound exam can be done in the office in as few as 5 minutes; often, evaluation of just a single joint will suffice. The time spent more than makes up for the time that would be needed to coordinate a referral to radiology and to follow up on that referral. And there are plenty of examples on how to successfully integrate ultrasound into your office workflow.

In summary, ultrasound should be used as an extension of our clinical examination. It allows for immediate imaging correlation, and it assists with decision making in an environment where radiology services have limitations. It is also phenomenally powerful when it comes to patient contact and education. True point-of-care ultrasound is fast, high quality, and cost efficient. If you show this information to patients, their families, taxpayers, and politicians, they will agree: There is no question that point-of-care ultrasound is the way to go.

Dr. Maggie Larché is a rheumatologist at St. Joseph’s Hospital and McMaster University Hospital, both in Hamilton, Ont. She is also vice president and treasurer of the Canadian Rheumatology Ultrasound Society. Dr. JohannesRoth is head of pediatric rheumatology at Children’s Hospital of Eastern Ontario, Ottawa, and is president of the Canadian Rheumatology Ultrasound Society. Dr. Larché disclosed no relevant conflicts of interest. Dr. Roth disclosed no relevant conflicts of interest.

COUNTERPOINT: Its use at present is best left to experts.

Ultrasound is an amazing tool, and we are not disputing its merits. Thus, the question is not so much whether it should be used in the rheumatologist’s office, but whether you should use it in your office.

Europe is often cited as a hotbed of ultrasound use in rheumatology to be emulated. But in fact, in only 10% of European countries do the majority of rheumatologists use ultrasound, and in no country do the majority of rheumatologists perform ultrasound-guided arthrocentesis (Rheumatol. 2012;51:184-90).

We don’t know if it is feasible to use ultrasound findings as outcome measures in routine clinical care. A recent systematic review noted the difficulty of determining the minimum number of joints to be included in a global ultrasound score and recommended further validation (J. Rheumatol. 2011;38:2055-62). The time needed to perform the exam ranged from 15 to 60 minutes.

Indeed, time and resource constraints are rightly cited as major barriers to wider use of ultrasound in the rheumatology office. Exam time is not the only consideration: The time to acquire ultrasound skills and then to maintain and improve them is also considerable. There is unquestionably a learning curve; it takes about 4-6 months to become good at this. Then you have to continually upgrade your skills.

Our patients already wait for care. If we begin doing ultrasound in the office, they will wait even longer to see us. This is important, as, for example, just a few months of early rheumatoid arthritis is destructive to the joints. Additionally, even with rheumatologists working at their current pace, there is already a projected shortfall of nearly two-thirds in the number needed in Canada by 2026 (J. Rheumatol. 2010;37:1749-55).

Ultrasound-guided needle placement in joint spaces sounds wonderful, but we need more long-term proof that it improves outcomes. For instance, when it comes to sacroiliac joint injections, clinical outcome is the same whether the needle is placed in the joint space or in the adjacent tissue (Rheumatology 2010;49:1479-82).

Ultrasound is incredibly subjective and user dependent. You need a lot of training to become good at it: There is only fair to moderate agreement in assessing synovitis for beginners just getting up to speed (Int. J. Rheumatol. 2010;164518). So unless you are an elite expert, you are not going to be that proficient, and there is potential for doing more harm than good.

In summary, point-of-care ultrasound in rheumatology needs more investigation. At present, we recommend against widespread adoption in rheumatologists’ offices. Rheumatologists’ time is too precious to waste on ultrasound exams. Even cardiologists and obstetrician-gynecologists have techs who do the exams; if we try to do them ourselves, our patient wait lists will skyrocket. The cost to you and society makes the choice clear: We should not be doing ultrasound routinely in our office.

Dr. Christopher Penney is a rheumatologist at Foothills Hospital in Calgary, Alta. Dr. David Collins is a rheumatologist at Vancouver (B.C.) General Hospital. Dr. Penney disclosed no relevant conflicts of interest. Dr. Collins disclosed no relevant conflicts of interest. The comments were based on presentations given at the annual meeting of the Canadian Rheumatology Association in Victoria, B.C.

POINT: All rheumatologists should offer it to their patients.

Like other point-of-care tests used all the time in medicine – spirometry, blood pressure measurement, the finger-stick glucose test – point-of-care ultrasound is invaluable in the diagnosis and management of rheumatologic conditions.

Ultrasound has a number of merits: It is portable and inexpensive; can be used on multiple joints; allows imaging of both bones and soft tissue, and assessment of vascularity; permits contralateral-side comparison; facilitates accurate injections; and serves as an informational and educational tool for patients. Contemporary machines have resolution down to 0.1 mm, much greater than the 1-2 mm for magnetic resonance imaging.

Photo: Susan London/IMNG Medical Media

A recent poll of Canadian rheumatologists about musculoskeletal ultrasound yielded some eye-opening findings. For example, 83% reported having to wait more than 2 weeks to obtain this exam if they referred patients to a radiology service, and just 56% reported that their radiology service offered assessment for inflammatory arthritis (Clin. Rheumatol. 2011;30:1277-83).

We know that information provided by ultrasound changes behavior in rheumatology: It leads to a change in diagnosis in 53% of patients and a change in management in 56% (Arthritis Rheum. 2001;44:2932-3). Ultrasound also improves diagnostic confidence in clinical findings (Skeletal Radiol. 2009;38:1049-54). Diagnostic certainty is key, as musculoskeletal symptoms are some of the most imprecise, and although we now have powerful medications for rheumatologic diseases, they don’t come cheap. Yet we are basing treatment decisions on clinical assessment alone. In an era of budget constraints, we owe it to patients and payers to make an accurate diagnosis and assessment: This is really all about providing an adequate standard of diagnosis and care.

In addition to aiding diagnosis, ultrasound helps in other ways, such as determining the risk of erosions (Arthritis Res. Ther. 2003;5:210-3) and predicting response to treatment (Arthritis Care Res. 2011;63:1477-81). It is more sensitive than clinical measures for assessing disease remission (Arthritis Rheum. 2008;58:2958-67). As patients have to live decades with their joints, and their quality of life is on the line, it is our responsibility to confirm clinically apparent remission with ultrasound.

An ultrasound exam can be done in the office in as few as 5 minutes; often, evaluation of just a single joint will suffice. The time spent more than makes up for the time that would be needed to coordinate a referral to radiology and to follow up on that referral. And there are plenty of examples on how to successfully integrate ultrasound into your office workflow.

In summary, ultrasound should be used as an extension of our clinical examination. It allows for immediate imaging correlation, and it assists with decision making in an environment where radiology services have limitations. It is also phenomenally powerful when it comes to patient contact and education. True point-of-care ultrasound is fast, high quality, and cost efficient. If you show this information to patients, their families, taxpayers, and politicians, they will agree: There is no question that point-of-care ultrasound is the way to go.

Dr. Maggie Larché is a rheumatologist at St. Joseph’s Hospital and McMaster University Hospital, both in Hamilton, Ont. She is also vice president and treasurer of the Canadian Rheumatology Ultrasound Society. Dr. JohannesRoth is head of pediatric rheumatology at Children’s Hospital of Eastern Ontario, Ottawa, and is president of the Canadian Rheumatology Ultrasound Society. Dr. Larché disclosed no relevant conflicts of interest. Dr. Roth disclosed no relevant conflicts of interest.

COUNTERPOINT: Its use at present is best left to experts.

Ultrasound is an amazing tool, and we are not disputing its merits. Thus, the question is not so much whether it should be used in the rheumatologist’s office, but whether you should use it in your office.

Europe is often cited as a hotbed of ultrasound use in rheumatology to be emulated. But in fact, in only 10% of European countries do the majority of rheumatologists use ultrasound, and in no country do the majority of rheumatologists perform ultrasound-guided arthrocentesis (Rheumatol. 2012;51:184-90).

We don’t know if it is feasible to use ultrasound findings as outcome measures in routine clinical care. A recent systematic review noted the difficulty of determining the minimum number of joints to be included in a global ultrasound score and recommended further validation (J. Rheumatol. 2011;38:2055-62). The time needed to perform the exam ranged from 15 to 60 minutes.

Indeed, time and resource constraints are rightly cited as major barriers to wider use of ultrasound in the rheumatology office. Exam time is not the only consideration: The time to acquire ultrasound skills and then to maintain and improve them is also considerable. There is unquestionably a learning curve; it takes about 4-6 months to become good at this. Then you have to continually upgrade your skills.

Our patients already wait for care. If we begin doing ultrasound in the office, they will wait even longer to see us. This is important, as, for example, just a few months of early rheumatoid arthritis is destructive to the joints. Additionally, even with rheumatologists working at their current pace, there is already a projected shortfall of nearly two-thirds in the number needed in Canada by 2026 (J. Rheumatol. 2010;37:1749-55).

Ultrasound-guided needle placement in joint spaces sounds wonderful, but we need more long-term proof that it improves outcomes. For instance, when it comes to sacroiliac joint injections, clinical outcome is the same whether the needle is placed in the joint space or in the adjacent tissue (Rheumatology 2010;49:1479-82).

Ultrasound is incredibly subjective and user dependent. You need a lot of training to become good at it: There is only fair to moderate agreement in assessing synovitis for beginners just getting up to speed (Int. J. Rheumatol. 2010;164518). So unless you are an elite expert, you are not going to be that proficient, and there is potential for doing more harm than good.

In summary, point-of-care ultrasound in rheumatology needs more investigation. At present, we recommend against widespread adoption in rheumatologists’ offices. Rheumatologists’ time is too precious to waste on ultrasound exams. Even cardiologists and obstetrician-gynecologists have techs who do the exams; if we try to do them ourselves, our patient wait lists will skyrocket. The cost to you and society makes the choice clear: We should not be doing ultrasound routinely in our office.

Dr. Christopher Penney is a rheumatologist at Foothills Hospital in Calgary, Alta. Dr. David Collins is a rheumatologist at Vancouver (B.C.) General Hospital. Dr. Penney disclosed no relevant conflicts of interest. Dr. Collins disclosed no relevant conflicts of interest. The comments were based on presentations given at the annual meeting of the Canadian Rheumatology Association in Victoria, B.C.

VICTORIA, B.C. – Autoantibodies directed against homocitrullinated fibrinogen may help identify patients with rheumatoid arthritis who would currently be missed, a study has shown.

A team led by Dr. Lillian Barra and Dr. Ewa Cairns of the University of Western Ontario, London, tested 84 patients with rheumatoid arthritis (RA) and found that nearly half had antihomocitrullinated fibrinogen antibodies (AHFAs) in their serum.

Perhaps most importantly, these antibodies were present in almost a fifth of patients who did not have anticitrullinated fibrinogen antibodies (ACFAs) and would thus have otherwise been considered to be seronegative.

The results also indicated that AHFAs were specific for RA: They were seldom found in 37 patients with systemic lupus erythematosus and 37 patients with psoriatic arthritis. And they were not found at all in any of 27 healthy volunteers.

These findings add to similar results seen in a cohort of patients from Leiden, the Netherlands (Proc. Natl. Acad. Sci. USA 2011;108:17372-7), noted Dr. Barra, who presented the findings at the annual meeting of the Canadian Rheumatology Association "This is an exploratory study, and we are going to do a lot of future work looking at these antibodies in a larger cohort, hopefully the CATCH [Canadian Arthritis Cohort]," she said.

The large collective group of anticitrullinated protein antibodies (ACPAs) target citrullinated proteins, such as the collagen, fibrinogen, and vimentin found in joint synovial fluid. "They are highly specific for rheumatoid arthritis and have been included in the new [American College of Rheumatology]-EULAR criteria" for diagnosing early disease, Dr. Barra pointed out.

ACPAs associate with the shared epitope, the strongest genetic risk factor for RA, and have been found to be pathogenic in mice, she further noted. "However, nearly 50% of patients with early rheumatoid arthritis do not have ACPAs, which begs the question of whether these patients have a different type of antibody that we don’t know about."

The investigators recruited patients meeting diagnostic criteria for various rheumatologic diseases from St. Joseph’s Health Care in Southwestern Ontario, nearly all of whom were white. They also recruited age- and sex-matched healthy volunteers.

Descriptive data indicated that, on average, the patients with rheumatoid arthritis had had their disease for about 9 years and had 4.3 swollen joints, Dr. Barra reported. Fifty-six percent were in remission.

The main study results showed that 49% of patients with rheumatoid arthritis overall had AHFAs. This compared with just 5% of patients with SLE, 3% of patients with psoriatic arthritis, and none of the healthy volunteers.

A full 31% of the patients with RA were negative for ACFAs, but 19% of this subgroup were found to have AHFAs. Viewed another way, 6% of the patients with RA overall were negative for ACFAs but positive for AHFAs. "These patients were previously considered seronegative, but they do have an antibody," Dr. Barra commented.

The investigators also used a computer algorithm to assess whether the proteins and peptides that are homocitrullinated would bind to the shared epitope. The results indicated that 35 of them, only 5 of which could also be citrullinated, would bind with high affinity. "This suggests that there are unique homocitrullinated peptides, but there is also the possibility of cross-reactivity" between AHFAs and ACFAs, she explained.

"We are going to investigate cross-reactivity further, and we would like to look at the immune responses [to these proteins] in vivo in future work," Dr. Barra concluded.

Dr. Barra said she had no relevant financial disclosures.

VICTORIA, B.C. – Autoantibodies directed against homocitrullinated fibrinogen may help identify patients with rheumatoid arthritis who would currently be missed, a study has shown.

A team led by Dr. Lillian Barra and Dr. Ewa Cairns of the University of Western Ontario, London, tested 84 patients with rheumatoid arthritis (RA) and found that nearly half had antihomocitrullinated fibrinogen antibodies (AHFAs) in their serum.

Perhaps most importantly, these antibodies were present in almost a fifth of patients who did not have anticitrullinated fibrinogen antibodies (ACFAs) and would thus have otherwise been considered to be seronegative.

The results also indicated that AHFAs were specific for RA: They were seldom found in 37 patients with systemic lupus erythematosus and 37 patients with psoriatic arthritis. And they were not found at all in any of 27 healthy volunteers.

These findings add to similar results seen in a cohort of patients from Leiden, the Netherlands (Proc. Natl. Acad. Sci. USA 2011;108:17372-7), noted Dr. Barra, who presented the findings at the annual meeting of the Canadian Rheumatology Association "This is an exploratory study, and we are going to do a lot of future work looking at these antibodies in a larger cohort, hopefully the CATCH [Canadian Arthritis Cohort]," she said.

The large collective group of anticitrullinated protein antibodies (ACPAs) target citrullinated proteins, such as the collagen, fibrinogen, and vimentin found in joint synovial fluid. "They are highly specific for rheumatoid arthritis and have been included in the new [American College of Rheumatology]-EULAR criteria" for diagnosing early disease, Dr. Barra pointed out.

ACPAs associate with the shared epitope, the strongest genetic risk factor for RA, and have been found to be pathogenic in mice, she further noted. "However, nearly 50% of patients with early rheumatoid arthritis do not have ACPAs, which begs the question of whether these patients have a different type of antibody that we don’t know about."

The investigators recruited patients meeting diagnostic criteria for various rheumatologic diseases from St. Joseph’s Health Care in Southwestern Ontario, nearly all of whom were white. They also recruited age- and sex-matched healthy volunteers.

Descriptive data indicated that, on average, the patients with rheumatoid arthritis had had their disease for about 9 years and had 4.3 swollen joints, Dr. Barra reported. Fifty-six percent were in remission.

The main study results showed that 49% of patients with rheumatoid arthritis overall had AHFAs. This compared with just 5% of patients with SLE, 3% of patients with psoriatic arthritis, and none of the healthy volunteers.

A full 31% of the patients with RA were negative for ACFAs, but 19% of this subgroup were found to have AHFAs. Viewed another way, 6% of the patients with RA overall were negative for ACFAs but positive for AHFAs. "These patients were previously considered seronegative, but they do have an antibody," Dr. Barra commented.

The investigators also used a computer algorithm to assess whether the proteins and peptides that are homocitrullinated would bind to the shared epitope. The results indicated that 35 of them, only 5 of which could also be citrullinated, would bind with high affinity. "This suggests that there are unique homocitrullinated peptides, but there is also the possibility of cross-reactivity" between AHFAs and ACFAs, she explained.

"We are going to investigate cross-reactivity further, and we would like to look at the immune responses [to these proteins] in vivo in future work," Dr. Barra concluded.

Dr. Barra said she had no relevant financial disclosures.

VICTORIA, B.C. – Autoantibodies directed against homocitrullinated fibrinogen may help identify patients with rheumatoid arthritis who would currently be missed, a study has shown.

A team led by Dr. Lillian Barra and Dr. Ewa Cairns of the University of Western Ontario, London, tested 84 patients with rheumatoid arthritis (RA) and found that nearly half had antihomocitrullinated fibrinogen antibodies (AHFAs) in their serum.

Perhaps most importantly, these antibodies were present in almost a fifth of patients who did not have anticitrullinated fibrinogen antibodies (ACFAs) and would thus have otherwise been considered to be seronegative.

The results also indicated that AHFAs were specific for RA: They were seldom found in 37 patients with systemic lupus erythematosus and 37 patients with psoriatic arthritis. And they were not found at all in any of 27 healthy volunteers.

These findings add to similar results seen in a cohort of patients from Leiden, the Netherlands (Proc. Natl. Acad. Sci. USA 2011;108:17372-7), noted Dr. Barra, who presented the findings at the annual meeting of the Canadian Rheumatology Association "This is an exploratory study, and we are going to do a lot of future work looking at these antibodies in a larger cohort, hopefully the CATCH [Canadian Arthritis Cohort]," she said.

The large collective group of anticitrullinated protein antibodies (ACPAs) target citrullinated proteins, such as the collagen, fibrinogen, and vimentin found in joint synovial fluid. "They are highly specific for rheumatoid arthritis and have been included in the new [American College of Rheumatology]-EULAR criteria" for diagnosing early disease, Dr. Barra pointed out.

ACPAs associate with the shared epitope, the strongest genetic risk factor for RA, and have been found to be pathogenic in mice, she further noted. "However, nearly 50% of patients with early rheumatoid arthritis do not have ACPAs, which begs the question of whether these patients have a different type of antibody that we don’t know about."

The investigators recruited patients meeting diagnostic criteria for various rheumatologic diseases from St. Joseph’s Health Care in Southwestern Ontario, nearly all of whom were white. They also recruited age- and sex-matched healthy volunteers.

Descriptive data indicated that, on average, the patients with rheumatoid arthritis had had their disease for about 9 years and had 4.3 swollen joints, Dr. Barra reported. Fifty-six percent were in remission.

The main study results showed that 49% of patients with rheumatoid arthritis overall had AHFAs. This compared with just 5% of patients with SLE, 3% of patients with psoriatic arthritis, and none of the healthy volunteers.

A full 31% of the patients with RA were negative for ACFAs, but 19% of this subgroup were found to have AHFAs. Viewed another way, 6% of the patients with RA overall were negative for ACFAs but positive for AHFAs. "These patients were previously considered seronegative, but they do have an antibody," Dr. Barra commented.

The investigators also used a computer algorithm to assess whether the proteins and peptides that are homocitrullinated would bind to the shared epitope. The results indicated that 35 of them, only 5 of which could also be citrullinated, would bind with high affinity. "This suggests that there are unique homocitrullinated peptides, but there is also the possibility of cross-reactivity" between AHFAs and ACFAs, she explained.

"We are going to investigate cross-reactivity further, and we would like to look at the immune responses [to these proteins] in vivo in future work," Dr. Barra concluded.

Dr. Barra said she had no relevant financial disclosures.

VICTORIA, B.C. – Individuals who have physically demanding occupations are at increased risk for osteoarthritis, even in this era of protective measures and equipment, a population-based study has shown.

In this study of a random sample of 88,202 noninstitutionalized U.S. adults, almost one in five reported having physician-diagnosed osteoarthritis (OA), Dr. Chengwei Wang reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

Photo ftwitty/iStockphoto.com

After adjustment for age, sex, ethnicity, and obesity, participants in physically demanding jobs such as building maintenance, health care support, and construction had significantly elevated risks of OA relative to their counterparts in computer and mathematical occupations (the group used for comparison because it had the lowest OA rate). The risk was increased to the greatest extent, essentially doubled, for those in military-specific occupations.

The risk of OA was significantly elevated for participants who were in office and administrative support occupations (relative risk, 1.24); sales and related occupations (1.28); building and grounds cleaning and maintenance (1.37); transportation and material moving (1.38); food preparation and serving (1.41); production (1.47); protective services (1.51); construction and extraction (1.51); health care support (1.54); installation, maintenance, and repair (1.54); and military-specific occupations (2.04).

These findings come from adjusted analyses of data from the U.S. National Health Interview Survey for the years 2005 through 2009 that used participants in computer and mathematical occupations as the reference group. Overall, 19.5% of the sample reported having physician-diagnosed OA.

"Doctors should know that people working in these occupations have a risk factor that plays an important role in developing osteoarthritis," Dr. Wang said in an interview. "I don’t think they need to change occupations. But doctors may want to tell patients to use some preventive measures when they work in these occupations other than to just prescribe medications" for musculoskeletal symptoms, she said.

"We need more-detailed studies to determine what kinds of factors in these occupations play a role in the development of this disease," such as various biomechanical factors, added Dr. Wang, a statistician at Nassau University Medical Center in East Meadow, N.Y. Additionally, the role of duration of exposure requires further investigation.

Such research could eventually help inform the redesign of workplaces and work practices to minimize risk, she said. For example, "occupational therapists and physical medicine and rehabilitation specialists could develop facilities to help protect workers in these occupations further," Dr. Wang suggested.

Dr. Wang said that she and her coauthors had no relevant financial disclosures.

VICTORIA, B.C. – Individuals who have physically demanding occupations are at increased risk for osteoarthritis, even in this era of protective measures and equipment, a population-based study has shown.

In this study of a random sample of 88,202 noninstitutionalized U.S. adults, almost one in five reported having physician-diagnosed osteoarthritis (OA), Dr. Chengwei Wang reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

Photo ftwitty/iStockphoto.com

After adjustment for age, sex, ethnicity, and obesity, participants in physically demanding jobs such as building maintenance, health care support, and construction had significantly elevated risks of OA relative to their counterparts in computer and mathematical occupations (the group used for comparison because it had the lowest OA rate). The risk was increased to the greatest extent, essentially doubled, for those in military-specific occupations.

The risk of OA was significantly elevated for participants who were in office and administrative support occupations (relative risk, 1.24); sales and related occupations (1.28); building and grounds cleaning and maintenance (1.37); transportation and material moving (1.38); food preparation and serving (1.41); production (1.47); protective services (1.51); construction and extraction (1.51); health care support (1.54); installation, maintenance, and repair (1.54); and military-specific occupations (2.04).

These findings come from adjusted analyses of data from the U.S. National Health Interview Survey for the years 2005 through 2009 that used participants in computer and mathematical occupations as the reference group. Overall, 19.5% of the sample reported having physician-diagnosed OA.

"Doctors should know that people working in these occupations have a risk factor that plays an important role in developing osteoarthritis," Dr. Wang said in an interview. "I don’t think they need to change occupations. But doctors may want to tell patients to use some preventive measures when they work in these occupations other than to just prescribe medications" for musculoskeletal symptoms, she said.

"We need more-detailed studies to determine what kinds of factors in these occupations play a role in the development of this disease," such as various biomechanical factors, added Dr. Wang, a statistician at Nassau University Medical Center in East Meadow, N.Y. Additionally, the role of duration of exposure requires further investigation.

Such research could eventually help inform the redesign of workplaces and work practices to minimize risk, she said. For example, "occupational therapists and physical medicine and rehabilitation specialists could develop facilities to help protect workers in these occupations further," Dr. Wang suggested.

Dr. Wang said that she and her coauthors had no relevant financial disclosures.

VICTORIA, B.C. – Individuals who have physically demanding occupations are at increased risk for osteoarthritis, even in this era of protective measures and equipment, a population-based study has shown.

In this study of a random sample of 88,202 noninstitutionalized U.S. adults, almost one in five reported having physician-diagnosed osteoarthritis (OA), Dr. Chengwei Wang reported in a poster session at the annual meeting of the Canadian Rheumatology Association.

Photo ftwitty/iStockphoto.com

After adjustment for age, sex, ethnicity, and obesity, participants in physically demanding jobs such as building maintenance, health care support, and construction had significantly elevated risks of OA relative to their counterparts in computer and mathematical occupations (the group used for comparison because it had the lowest OA rate). The risk was increased to the greatest extent, essentially doubled, for those in military-specific occupations.

The risk of OA was significantly elevated for participants who were in office and administrative support occupations (relative risk, 1.24); sales and related occupations (1.28); building and grounds cleaning and maintenance (1.37); transportation and material moving (1.38); food preparation and serving (1.41); production (1.47); protective services (1.51); construction and extraction (1.51); health care support (1.54); installation, maintenance, and repair (1.54); and military-specific occupations (2.04).

These findings come from adjusted analyses of data from the U.S. National Health Interview Survey for the years 2005 through 2009 that used participants in computer and mathematical occupations as the reference group. Overall, 19.5% of the sample reported having physician-diagnosed OA.

"Doctors should know that people working in these occupations have a risk factor that plays an important role in developing osteoarthritis," Dr. Wang said in an interview. "I don’t think they need to change occupations. But doctors may want to tell patients to use some preventive measures when they work in these occupations other than to just prescribe medications" for musculoskeletal symptoms, she said.

"We need more-detailed studies to determine what kinds of factors in these occupations play a role in the development of this disease," such as various biomechanical factors, added Dr. Wang, a statistician at Nassau University Medical Center in East Meadow, N.Y. Additionally, the role of duration of exposure requires further investigation.

Such research could eventually help inform the redesign of workplaces and work practices to minimize risk, she said. For example, "occupational therapists and physical medicine and rehabilitation specialists could develop facilities to help protect workers in these occupations further," Dr. Wang suggested.

Dr. Wang said that she and her coauthors had no relevant financial disclosures.

VICTORIA, B.C. – Some patients with systemic lupus erythematosus may be more likely than others to experience a prolonged remission, new data suggest.

In a study of more than 1,500 patients who had SLE, about 2% achieved a remission lasting at least 5 years on either no medication or only antimalarial drugs, Anjali Papneja reported at the annual meeting of the Canadian Rheumatology Association.

The prolonged remissions lasted on average almost 12 years. Nearly a third of the patients had had a monophasic clinical disease course, characterized by only a single flare, before their remission.

Patients achieving a prolonged remission were more likely to be white, had milder disease, and were less likely to have involvement of certain organ systems and to have received steroids or other immunosuppressive agents prior to remission onset.

"Prolonged remission is an infrequent outcome among SLE patients, but it generally lasts for over a decade, and it is preceded by an atypically monophasic clinical course in a significant minority," Ms. Papneja commented.

"We want to know what makes these patients different, how they can be treated most effectively, and how we can harness this unique and desirable outcome more generally," she added.

An attendee asked what the remission rate was if patients who achieved remission on stable immunosuppressive regimens and/or low-dose prednisone were also included.

The reason for including only those patients who had remitted off all steroids and immunosuppressive agents was to distinguish those whose SLE was in true remission (i.e., those in the cohort), from those whose disease was merely suppressed by the ongoing use of these medications, replied Ms. Papneja, a medical student at the University of Toronto. "But they do remain on antimalarials because in recent decades, it has been found that these patients have cardiovascular protective benefits from antimalarials."

The investigators studied all patients with SLE followed at the university’s Lupus Clinic from July 1970 through May 2011.

Patients were defined as having a prolonged remission if they did not have any clinical disease activity for at least 5 years, had regular clinic visits, and received no immunosuppressive medications or at most antimalarial drugs during the remission.

With a mean duration of follow-up of nearly 22 years, 2.4% of the 1,613 patients studied achieved a prolonged remission, after a mean disease duration of about 9 years. These sustained remissions lasted an average of nearly 12 years.

By type, 44% of the remissions were serologically and clinically quiescent, 28% were serologically active but clinically quiescent, and 28% fluctuated between these types.

In the years leading up to the remission, the majority of patients (71%) had a relapsing-remitting clinical course, but a sizable proportion (29%) had a monophasic course. "It’s worthwhile to study these patients further to determine at what point we can safely define a disease course as being monophasic," Ms. Papneja commented. None of the patients achieving prolonged remission had a chronic active course.

In a case-control comparison, in which each patient who achieved prolonged remission was matched with three who did not, the former were more likely to be white (82% vs. 72%), had a lower SLE Disease Activity Index (SLEDAI-2K) score at their first clinic visit (8 vs. 10.6), and had a lower adjusted mean SLEDAI-2K score in the 3 years leading up to remission (3 vs. 5.9).

The group achieving prolonged remission was also significantly less likely to have skin, pulmonary, and central nervous system involvement, but "we noted that there was no difference in renal involvement between cases and controls," she pointed out. Additionally, they were less likely to have received steroids (58% vs. 80%) and other immunosuppressive agents (24% vs. 47%) prior to remission onset, also seeming to point to milder disease.

A study limitation, Ms. Papneja acknowledged, was that only patients continuing care at the clinic were included, and the clinic’s attrition rate was about 10%. Thus, some patients achieving remission and dropping out of care, or having a flare and seeking treatment elsewhere, may have been lost to follow-up.

Ms. Papneja disclosed that she had no relevant conflicts of interest.

VICTORIA, B.C. – Some patients with systemic lupus erythematosus may be more likely than others to experience a prolonged remission, new data suggest.

In a study of more than 1,500 patients who had SLE, about 2% achieved a remission lasting at least 5 years on either no medication or only antimalarial drugs, Anjali Papneja reported at the annual meeting of the Canadian Rheumatology Association.

The prolonged remissions lasted on average almost 12 years. Nearly a third of the patients had had a monophasic clinical disease course, characterized by only a single flare, before their remission.

Patients achieving a prolonged remission were more likely to be white, had milder disease, and were less likely to have involvement of certain organ systems and to have received steroids or other immunosuppressive agents prior to remission onset.

"Prolonged remission is an infrequent outcome among SLE patients, but it generally lasts for over a decade, and it is preceded by an atypically monophasic clinical course in a significant minority," Ms. Papneja commented.

"We want to know what makes these patients different, how they can be treated most effectively, and how we can harness this unique and desirable outcome more generally," she added.

An attendee asked what the remission rate was if patients who achieved remission on stable immunosuppressive regimens and/or low-dose prednisone were also included.

The reason for including only those patients who had remitted off all steroids and immunosuppressive agents was to distinguish those whose SLE was in true remission (i.e., those in the cohort), from those whose disease was merely suppressed by the ongoing use of these medications, replied Ms. Papneja, a medical student at the University of Toronto. "But they do remain on antimalarials because in recent decades, it has been found that these patients have cardiovascular protective benefits from antimalarials."

The investigators studied all patients with SLE followed at the university’s Lupus Clinic from July 1970 through May 2011.

Patients were defined as having a prolonged remission if they did not have any clinical disease activity for at least 5 years, had regular clinic visits, and received no immunosuppressive medications or at most antimalarial drugs during the remission.

With a mean duration of follow-up of nearly 22 years, 2.4% of the 1,613 patients studied achieved a prolonged remission, after a mean disease duration of about 9 years. These sustained remissions lasted an average of nearly 12 years.

By type, 44% of the remissions were serologically and clinically quiescent, 28% were serologically active but clinically quiescent, and 28% fluctuated between these types.

In the years leading up to the remission, the majority of patients (71%) had a relapsing-remitting clinical course, but a sizable proportion (29%) had a monophasic course. "It’s worthwhile to study these patients further to determine at what point we can safely define a disease course as being monophasic," Ms. Papneja commented. None of the patients achieving prolonged remission had a chronic active course.

In a case-control comparison, in which each patient who achieved prolonged remission was matched with three who did not, the former were more likely to be white (82% vs. 72%), had a lower SLE Disease Activity Index (SLEDAI-2K) score at their first clinic visit (8 vs. 10.6), and had a lower adjusted mean SLEDAI-2K score in the 3 years leading up to remission (3 vs. 5.9).

The group achieving prolonged remission was also significantly less likely to have skin, pulmonary, and central nervous system involvement, but "we noted that there was no difference in renal involvement between cases and controls," she pointed out. Additionally, they were less likely to have received steroids (58% vs. 80%) and other immunosuppressive agents (24% vs. 47%) prior to remission onset, also seeming to point to milder disease.

A study limitation, Ms. Papneja acknowledged, was that only patients continuing care at the clinic were included, and the clinic’s attrition rate was about 10%. Thus, some patients achieving remission and dropping out of care, or having a flare and seeking treatment elsewhere, may have been lost to follow-up.

Ms. Papneja disclosed that she had no relevant conflicts of interest.

VICTORIA, B.C. – Some patients with systemic lupus erythematosus may be more likely than others to experience a prolonged remission, new data suggest.

In a study of more than 1,500 patients who had SLE, about 2% achieved a remission lasting at least 5 years on either no medication or only antimalarial drugs, Anjali Papneja reported at the annual meeting of the Canadian Rheumatology Association.

The prolonged remissions lasted on average almost 12 years. Nearly a third of the patients had had a monophasic clinical disease course, characterized by only a single flare, before their remission.

Patients achieving a prolonged remission were more likely to be white, had milder disease, and were less likely to have involvement of certain organ systems and to have received steroids or other immunosuppressive agents prior to remission onset.

"Prolonged remission is an infrequent outcome among SLE patients, but it generally lasts for over a decade, and it is preceded by an atypically monophasic clinical course in a significant minority," Ms. Papneja commented.

"We want to know what makes these patients different, how they can be treated most effectively, and how we can harness this unique and desirable outcome more generally," she added.

An attendee asked what the remission rate was if patients who achieved remission on stable immunosuppressive regimens and/or low-dose prednisone were also included.

The reason for including only those patients who had remitted off all steroids and immunosuppressive agents was to distinguish those whose SLE was in true remission (i.e., those in the cohort), from those whose disease was merely suppressed by the ongoing use of these medications, replied Ms. Papneja, a medical student at the University of Toronto. "But they do remain on antimalarials because in recent decades, it has been found that these patients have cardiovascular protective benefits from antimalarials."

The investigators studied all patients with SLE followed at the university’s Lupus Clinic from July 1970 through May 2011.

Patients were defined as having a prolonged remission if they did not have any clinical disease activity for at least 5 years, had regular clinic visits, and received no immunosuppressive medications or at most antimalarial drugs during the remission.

With a mean duration of follow-up of nearly 22 years, 2.4% of the 1,613 patients studied achieved a prolonged remission, after a mean disease duration of about 9 years. These sustained remissions lasted an average of nearly 12 years.

By type, 44% of the remissions were serologically and clinically quiescent, 28% were serologically active but clinically quiescent, and 28% fluctuated between these types.

In the years leading up to the remission, the majority of patients (71%) had a relapsing-remitting clinical course, but a sizable proportion (29%) had a monophasic course. "It’s worthwhile to study these patients further to determine at what point we can safely define a disease course as being monophasic," Ms. Papneja commented. None of the patients achieving prolonged remission had a chronic active course.

In a case-control comparison, in which each patient who achieved prolonged remission was matched with three who did not, the former were more likely to be white (82% vs. 72%), had a lower SLE Disease Activity Index (SLEDAI-2K) score at their first clinic visit (8 vs. 10.6), and had a lower adjusted mean SLEDAI-2K score in the 3 years leading up to remission (3 vs. 5.9).

The group achieving prolonged remission was also significantly less likely to have skin, pulmonary, and central nervous system involvement, but "we noted that there was no difference in renal involvement between cases and controls," she pointed out. Additionally, they were less likely to have received steroids (58% vs. 80%) and other immunosuppressive agents (24% vs. 47%) prior to remission onset, also seeming to point to milder disease.

A study limitation, Ms. Papneja acknowledged, was that only patients continuing care at the clinic were included, and the clinic’s attrition rate was about 10%. Thus, some patients achieving remission and dropping out of care, or having a flare and seeking treatment elsewhere, may have been lost to follow-up.

Ms. Papneja disclosed that she had no relevant conflicts of interest.

Biologic agents that block the action of tumor necrosis factor have dramatically improved patient outcomes. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

Biologic agents that block the action of tumor necrosis factor have dramatically improved patient outcomes. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

Biologic agents that block the action of tumor necrosis factor have dramatically improved patient outcomes. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

Biologic agents that block the action of tumor necrosis factor have dramatically improved outcomes in rheumatoid arthritis. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

Rheumatoid arthritis is increasingly recognized to be a highly cellularly and molecularly diverse collection of entities having essentially the same clinical picture, as is evident from varied treatment responses. In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment of rheumatoid arthritis. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

Biologic agents that block the action of tumor necrosis factor have dramatically improved outcomes in rheumatoid arthritis. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

Rheumatoid arthritis is increasingly recognized to be a highly cellularly and molecularly diverse collection of entities having essentially the same clinical picture, as is evident from varied treatment responses. In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment of rheumatoid arthritis. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

Biologic agents that block the action of tumor necrosis factor have dramatically improved outcomes in rheumatoid arthritis. But they sometimes have little effect or lose effectiveness over time, necessitating a change in therapy. Emerging evidence, recently incorporated into a treatment algorithm, is helping to guide selection of the next biologic for such patients in a rational, personalized way (Rheumatology 2012;51:600-9).

Primary vs. Secondary Nonresponse

The first key consideration in selecting the next therapy is whether the patient has primary or secondary nonresponse to the anti-TNF agent, as this influences the odds of response to another agent in this class. The distinction is not clear-cut, but generally, primary nonresponse manifests 12-16 weeks after starting the agent, whereas secondary nonresponse emerges after 6-12 months.

Rheumatoid arthritis is increasingly recognized to be a highly cellularly and molecularly diverse collection of entities having essentially the same clinical picture, as is evident from varied treatment responses. In the context of anti-TNF therapy, compared with their counterparts having a response, primary nonresponders appear to have disease that is less dependent on TNF and to have a lower proinflammatory gene profile in the synovium.

In contrast, the reason for secondary nonresponse is usually unrelated to the disease process, and instead often is due to the development of antibodies against the TNF blocker – either human antichimeric antibodies (HACAs), as in the case of infliximab (Remicade), or human antihuman antibodies (HAHAs), as in the case of adalimumab (Humira).

Thus, primary nonresponders to TNF blockers are less likely to respond to other agents in this class, whereas secondary nonresponders seem to respond almost as well as patients who have never been given one of these agents before (EULAR 2008, abstract FRI0125).

Presence vs. Absence of Autoantibodies

The second key consideration after failure of a TNF blocker is whether the patient has autoantibodies, specifically, rheumatoid factor and/or anti–citrullinated protein antibodies (ACPAs), as their presence influences the odds of response to the B cell–depleting agent rituximab (Rituxan).

Autoantibody-positive patients have a better response than their autoantibody-negative counterparts to rituximab (EULAR 2009, abstract FRI0256). Occasionally, patients who appear to be autoantibody negative still benefit, likely because they have autoantibodies that we cannot yet detect.

Taken together, current data suggest that among primary anti-TNF nonresponders, patients who are autoantibody positive are most likely to benefit from three agents having other mechanisms of action: rituximab; abatacept (Orencia), a T-cell costimulation modulator; and tocilizumab (Actemra), an antibody to the interleukin-6 receptor. Those who are antibody negative are more likely to benefit only from abatacept or tocilizumab.

Among secondary nonresponders, patients who are autoantibody positive appear to have the most options – another anti-TNF agent, rituximab, abatacept, and tocilizumab – whereas those who are autoantibody negative are likely to benefit from any of these agents except rituximab.

Future Directions

We may be able to refine this personalized approach in the future. For example, the type 1 interferon signature may protect against rituximab-induced B cell depletion, as a higher signature in peripheral blood is associated with a lack of clinical response to this agent (Arthritis Rheum. 2010;62:3607-14). There may well be other predictive markers too, so we may one day be able to apply a multimarker panel in the clinic.

Also, additional treatment factors being identified may help guide the selection among multiple agents. For instance, a patient’s ability to take methotrexate, often given in combination with biologics, may play a role, as evidence suggests that tocilizumab given as monotherapy is just as effective as combinations of TNF blockers with methotrexate.

Identification of predictive biomarkers, while challenging and expensive, will help to optimize treatment of rheumatoid arthritis. There is a very clear need to come up with a much more sophisticated approach as opposed to the current one based on clinical measures. There has been progress in this area, but we need to continue to invest in biomarker research because this is really a more rational approach and the way forward.

Dr. Tak is professor of medicine at the AMC/University of Amsterdam and Senior Vice President/Head, Therapy Area Immunoinflammation at GlaxoSmithKline. He disclosed that he has been a consultant to Abbott, Amgen, Merck, Pfizer, and Roche/Genentech.

VICTORIA, B.C. – Patients with rheumatoid arthritis who achieve remission on an agent targeting tumor necrosis factor have improvements in a variety of measures of resource use, activities of daily living, and employment, data have shown.

Investigators led by Dr. Cheryl Barnabe, a rheumatologist at the University of Calgary (Alta.), analyzed data from the Alberta Biologics Pharmacosurveillance Program for 1,315 patients with rheumatoid arthritis (RA) treated with a monoclonal antibody to tumor necrosis factor (TNF).

"Even in this patient group with severe disease and long disease duration, 34% were able to achieve remission in their first year of anti-TNF therapy, and an additional 25% were able to achieve minimal disease activity," she reported at the annual meeting of the Canadian Rheumatology Association.

Compared with their counterparts who had continued moderate or high disease activity, these patients had roughly one-third to three-fourths reductions in rates of limitations of daily activities, hospitalization, and curtailed work hours, and in over-the-counter drug costs.

The group who improved to the point of having minimal disease activity on therapy also had comparatively better outcomes, although the differences were generally smaller.

"The patients who achieved remission had benefits over those who had only attained minimal disease activity, implicating that our treatment goal should be remission and not just minimal disease activity," Dr. Barnabe said.

The Alberta Biologics Pharmacosurveillance Program prospectively collected data on safety, efficacy, function, quality of life, and resource use among patients with RA treated with anti-TNF biologics between April 2004 and March 2011. Costs to the health care system were ascertained by linking to the provincial health care utilization database.

Patients’ clinical response was defined as remission, minimal disease activity, or moderate-to-high disease activity using established assessment tools. The investigators compared outcomes for patients in their first year of a first anti-TNF therapy.

On average, the patients were 42 years old at diagnosis and had had RA for 14 years, Dr. Barnabe reported. The median number of disease-modifying antirheumatic drugs they had received was three. Their mean 28-joint Disease Activity Score at treatment start was 5.93.

The anti-TNF agent administered was etanercept (Enbrel) in 55% of patients, infliximab (Remicade) in 22%, adalimumab (Humira) in 18%, golimumab (Simponi) in 4%, and certolizumab (Cimzia) in 1%.

Compared with other patients, those who achieved remission in the first year of therapy had lower measures of inflammation, disease activity, and pain at baseline, according to Dr. Barnabe. However, they were similar with respect to measures of resource use, activities of daily living, and employment.

The main results showed that relative to their counterparts who had continued moderate-to-high disease activity, patients achieving remission were significantly less likely to have had a recent hospitalization (5% vs. 8%), had lower monthly costs for over-the-counter drugs ($15 vs. $59), and were less likely to have been unable to do usual activities in the past month (28% vs. 52%), to have needed help from others with activities of daily living in the past month (18% vs. 39%), and to have had to reduce their work hours in the past 6 months because of poor health (2% vs. 7%).

Patients achieving minimal disease activity also fared better than those with continued moderate-to-high disease activity, although benefits were smaller, according to Dr. Barnabe.

The disease response groups were statistically indistinguishable with respect to some other outcomes, such as outpatient visits, diagnostic tests, the use of community services, missed days of work, and the need to stop work or retire early because of arthritis.

Dr. Barnabe disclosed financial relationships with Abbott, Amgen/Pfizer, Bristol-Myers Squibb, and UCB. The program had independent multisource industry funding between 2009 and 2012.

VICTORIA, B.C. – Patients with rheumatoid arthritis who achieve remission on an agent targeting tumor necrosis factor have improvements in a variety of measures of resource use, activities of daily living, and employment, data have shown.

Investigators led by Dr. Cheryl Barnabe, a rheumatologist at the University of Calgary (Alta.), analyzed data from the Alberta Biologics Pharmacosurveillance Program for 1,315 patients with rheumatoid arthritis (RA) treated with a monoclonal antibody to tumor necrosis factor (TNF).

"Even in this patient group with severe disease and long disease duration, 34% were able to achieve remission in their first year of anti-TNF therapy, and an additional 25% were able to achieve minimal disease activity," she reported at the annual meeting of the Canadian Rheumatology Association.

Compared with their counterparts who had continued moderate or high disease activity, these patients had roughly one-third to three-fourths reductions in rates of limitations of daily activities, hospitalization, and curtailed work hours, and in over-the-counter drug costs.

The group who improved to the point of having minimal disease activity on therapy also had comparatively better outcomes, although the differences were generally smaller.

"The patients who achieved remission had benefits over those who had only attained minimal disease activity, implicating that our treatment goal should be remission and not just minimal disease activity," Dr. Barnabe said.

The Alberta Biologics Pharmacosurveillance Program prospectively collected data on safety, efficacy, function, quality of life, and resource use among patients with RA treated with anti-TNF biologics between April 2004 and March 2011. Costs to the health care system were ascertained by linking to the provincial health care utilization database.

Patients’ clinical response was defined as remission, minimal disease activity, or moderate-to-high disease activity using established assessment tools. The investigators compared outcomes for patients in their first year of a first anti-TNF therapy.

On average, the patients were 42 years old at diagnosis and had had RA for 14 years, Dr. Barnabe reported. The median number of disease-modifying antirheumatic drugs they had received was three. Their mean 28-joint Disease Activity Score at treatment start was 5.93.

The anti-TNF agent administered was etanercept (Enbrel) in 55% of patients, infliximab (Remicade) in 22%, adalimumab (Humira) in 18%, golimumab (Simponi) in 4%, and certolizumab (Cimzia) in 1%.

Compared with other patients, those who achieved remission in the first year of therapy had lower measures of inflammation, disease activity, and pain at baseline, according to Dr. Barnabe. However, they were similar with respect to measures of resource use, activities of daily living, and employment.

The main results showed that relative to their counterparts who had continued moderate-to-high disease activity, patients achieving remission were significantly less likely to have had a recent hospitalization (5% vs. 8%), had lower monthly costs for over-the-counter drugs ($15 vs. $59), and were less likely to have been unable to do usual activities in the past month (28% vs. 52%), to have needed help from others with activities of daily living in the past month (18% vs. 39%), and to have had to reduce their work hours in the past 6 months because of poor health (2% vs. 7%).

Patients achieving minimal disease activity also fared better than those with continued moderate-to-high disease activity, although benefits were smaller, according to Dr. Barnabe.

The disease response groups were statistically indistinguishable with respect to some other outcomes, such as outpatient visits, diagnostic tests, the use of community services, missed days of work, and the need to stop work or retire early because of arthritis.

Dr. Barnabe disclosed financial relationships with Abbott, Amgen/Pfizer, Bristol-Myers Squibb, and UCB. The program had independent multisource industry funding between 2009 and 2012.

VICTORIA, B.C. – Patients with rheumatoid arthritis who achieve remission on an agent targeting tumor necrosis factor have improvements in a variety of measures of resource use, activities of daily living, and employment, data have shown.

Investigators led by Dr. Cheryl Barnabe, a rheumatologist at the University of Calgary (Alta.), analyzed data from the Alberta Biologics Pharmacosurveillance Program for 1,315 patients with rheumatoid arthritis (RA) treated with a monoclonal antibody to tumor necrosis factor (TNF).

"Even in this patient group with severe disease and long disease duration, 34% were able to achieve remission in their first year of anti-TNF therapy, and an additional 25% were able to achieve minimal disease activity," she reported at the annual meeting of the Canadian Rheumatology Association.

Compared with their counterparts who had continued moderate or high disease activity, these patients had roughly one-third to three-fourths reductions in rates of limitations of daily activities, hospitalization, and curtailed work hours, and in over-the-counter drug costs.

The group who improved to the point of having minimal disease activity on therapy also had comparatively better outcomes, although the differences were generally smaller.

"The patients who achieved remission had benefits over those who had only attained minimal disease activity, implicating that our treatment goal should be remission and not just minimal disease activity," Dr. Barnabe said.

The Alberta Biologics Pharmacosurveillance Program prospectively collected data on safety, efficacy, function, quality of life, and resource use among patients with RA treated with anti-TNF biologics between April 2004 and March 2011. Costs to the health care system were ascertained by linking to the provincial health care utilization database.

Patients’ clinical response was defined as remission, minimal disease activity, or moderate-to-high disease activity using established assessment tools. The investigators compared outcomes for patients in their first year of a first anti-TNF therapy.

On average, the patients were 42 years old at diagnosis and had had RA for 14 years, Dr. Barnabe reported. The median number of disease-modifying antirheumatic drugs they had received was three. Their mean 28-joint Disease Activity Score at treatment start was 5.93.

The anti-TNF agent administered was etanercept (Enbrel) in 55% of patients, infliximab (Remicade) in 22%, adalimumab (Humira) in 18%, golimumab (Simponi) in 4%, and certolizumab (Cimzia) in 1%.

Compared with other patients, those who achieved remission in the first year of therapy had lower measures of inflammation, disease activity, and pain at baseline, according to Dr. Barnabe. However, they were similar with respect to measures of resource use, activities of daily living, and employment.

The main results showed that relative to their counterparts who had continued moderate-to-high disease activity, patients achieving remission were significantly less likely to have had a recent hospitalization (5% vs. 8%), had lower monthly costs for over-the-counter drugs ($15 vs. $59), and were less likely to have been unable to do usual activities in the past month (28% vs. 52%), to have needed help from others with activities of daily living in the past month (18% vs. 39%), and to have had to reduce their work hours in the past 6 months because of poor health (2% vs. 7%).

Patients achieving minimal disease activity also fared better than those with continued moderate-to-high disease activity, although benefits were smaller, according to Dr. Barnabe.

The disease response groups were statistically indistinguishable with respect to some other outcomes, such as outpatient visits, diagnostic tests, the use of community services, missed days of work, and the need to stop work or retire early because of arthritis.

Dr. Barnabe disclosed financial relationships with Abbott, Amgen/Pfizer, Bristol-Myers Squibb, and UCB. The program had independent multisource industry funding between 2009 and 2012.