Rheumatoid Arthritis

Major Finding: Methotrexate combined with other DMARDs prolonged anti-TNF therapy adherence in rheumatoid arthritis patients

Data Source: A prospective, observational cohort study of 10,396 adults with RA.

Disclosures: The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

Major Finding: Methotrexate combined with other DMARDs prolonged anti-TNF therapy adherence in rheumatoid arthritis patients

Data Source: A prospective, observational cohort study of 10,396 adults with RA.

Disclosures: The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

Major Finding: Methotrexate combined with other DMARDs prolonged anti-TNF therapy adherence in rheumatoid arthritis patients

Data Source: A prospective, observational cohort study of 10,396 adults with RA.

Disclosures: The study was funded by the British Society for Rheumatology, which receives some income from pharmaceutical companies including Abbott Laboratories, Amgen, Roche, Schering-Plough, and Wyeth Pharmaceuticals.

Patients who received methotrexate in combination with other disease-modifying antirheumatic drugs were significantly more likely to remain on anti–tumor necrosis factor therapy than were patients who received methotrexate monotherapy or other DMARDs without methotrexate, based on data from more than 10,000 patients in the British Society for Rheumatology Biologics Register.

Previous studies have examined the impact of DMARDs on the continuation of anti-TNF therapy, but most of these did not compare the effects of specific DMARDs, said Dr. Moetaza M. Soliman of the University of Manchester (England) and colleagues (Ann. Rheum. Dis. 2011 Feb. 17 [doi:10.1136/ard.2010.139774]).

After 5 years of follow-up, patients who received methotrexate (MTX) in combination with either sulfasalazine or hydroxychloroquine or a combination of the two agents were significantly less likely to discontinue anti-TNF therapy, compared with those who received MTX alone. The adjusted hazard ratios were 0.76, 0.81, and 0.80, respectively, compared with methotrexate alone.

Patients who received no DMARDs were 40% more likely to discontinue anti-TNF, compared with those who received MTX. Patients who received leflunomide or sulfasalazine were 41% and 23% more likely, respectively, to discontinue anti-TNF therapy, compared with those who received MTX.

The study population included 3,339 patients receiving no DMARDs, 4,418 on MTX, 610 taking leflunomide, 308 receiving sulfasalazine, 902 on MTX plus sulfasalazine, 401 taking MTX plus hydroxychloroquine, and 418 on MTX plus a sulfasalazine and hydroxychloroquine combination. The average age of the patients was 56 years, and the average disease duration was 13 years.

The results were similar when the researchers controlled for reasons for discontinuation, including adverse events and lack of efficacy. The results support the use of MTX alone or in combination with other DMARDs as a way to extend compliance with anti-TNF therapy, the researchers noted.

Major Finding: The use of disease-modifying antirheumatic drugs varies widely according to patient age, sex, and race; income; location; and health plan.

Data Source: An analysis of Healthcare Effectiveness Data and Information Set data on medication use in a nationally representative sample of 93,134 RA patients enrolled in Medicare managed care plans.

Disclosures: This study was supported by the American College of Rheumatology, National Center for Research Resources, Rosalind Russell Medical Research Centers for Arthritis, National Institutes of Health, State of California Lupus Fund, Arthritis Foundation, Agency for Healthcare Research and Quality, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. An associate of Dr. Schmajuk reported financial ties to Merck and the Pfizer Foundation.

Whether patients with rheumatoid arthritis receive appropriate antirheumatic medications varies widely and depends on their age, sex, race, income, the neighborhood and area of the country where they reside, and their health care plan, judging from recent study findings.

“Although RA was once an inevitably deforming and disabling condition, the development of new DMARDs [disease-modifying antirheumatic drugs] and support for their early use has dramatically improved clinical outcomes for many patients.

“This study suggests that one mechanism for the sociodemographic disparities in RA outcomes in the United States may relate to differences in DMARD receipt,” according to Dr. Gabriela Schmajuk of Stanford (Calif.) University and her associates.

Recent population-based studies have shown consistently low rates of DMARD use, even though evidence-based guidelines recommend early and aggressive treatment.

Dr. Schmajuk and her colleagues assessed medication use in a cohort of 93,143 RA patients enrolled in Medicare managed care plans during a recent 4-year period.

The cohort comprises a nationally representative sample of the managed care population aged 65 years and older.

Overall, 37% of patients were not receiving DMARDs.

These include abatacept, adalimumab, anakinra, azathioprine, cyclophosphamide, cyclosporine, etanercept, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, penicillamine, rituximab, staphylococcal protein A, and sulfasalazine.

In some cases, patients may have declined DMARD treatment, may have had quiescent disease that didn't require treatment, or may have had contraindications to all 17 of these drugs.

The greatest variation in the rate of DMARD use occurred by patient ag.

Only 42% of patients aged 85 years or older received DMARDs, compared with 72%, of those aged 65-69 years.

It is possible that older patients had more comorbidities limiting their ability to use these drugs.

It also is possible that age bias played a role in this result, according to the investigators.

Men had slightly lower rates of use than women, and patients self-identified as black or “other” had lower rates of use (57% and 58%, respectively) than white patients (64%).

The rate of DMARD use was 55% among patients with a low personal income, compared with 64% among those with higher incomes.

Similarly, patients who lived in neighborhoods of low socioeconomic status were less likely to be taking DMARDs than patients living in neighborhoods with higher socioeconomic status.

It is possible that some of these patients don't get DMARDs because they are unable to afford copayments or other forms of cost sharing, the investigators said.

Patients living in the South Atlantic and Middle Atlantic regions of the country had rates of use that were 10% lower than those living in other regions.

The use of DMARDs was 6% lower among patients who were enrolled in for-profit health plans than among those who were enrolled in not-for-profit plans, a difference that was small but statistically significant.

However, variability by health plan was much greater than that statistic alone would convey.

Rates of use of DMARDs varied from a low of 16% in one health plan to a high of 87% in another. This findings held true even after the data had been adjusted to account for differences in case mix.

This finding is “concerning,” Dr. Schmajuk and her associates said (JAMA 2011;305:480-6).

It is unknown whether this 70-point difference in DMARD use is due to differences in the availability or accessibility of specialty care within some health plans or differences in allowances on prescription drug benefits between health plans.

It may even reflect in part inaccurate reporting on the forms used to collect the data, they added.

Whatever the explanations, the large variations in DMARD use are “unacceptable,” the researchers said.

“Targeting educational and quality improvement interventions to patients who are underusing DMARDs and their clinicians will be important to eliminate these disparities,” they said.

Major Finding: The use of disease-modifying antirheumatic drugs varies widely according to patient age, sex, and race; income; location; and health plan.

Data Source: An analysis of Healthcare Effectiveness Data and Information Set data on medication use in a nationally representative sample of 93,134 RA patients enrolled in Medicare managed care plans.

Disclosures: This study was supported by the American College of Rheumatology, National Center for Research Resources, Rosalind Russell Medical Research Centers for Arthritis, National Institutes of Health, State of California Lupus Fund, Arthritis Foundation, Agency for Healthcare Research and Quality, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. An associate of Dr. Schmajuk reported financial ties to Merck and the Pfizer Foundation.

Whether patients with rheumatoid arthritis receive appropriate antirheumatic medications varies widely and depends on their age, sex, race, income, the neighborhood and area of the country where they reside, and their health care plan, judging from recent study findings.

“Although RA was once an inevitably deforming and disabling condition, the development of new DMARDs [disease-modifying antirheumatic drugs] and support for their early use has dramatically improved clinical outcomes for many patients.

“This study suggests that one mechanism for the sociodemographic disparities in RA outcomes in the United States may relate to differences in DMARD receipt,” according to Dr. Gabriela Schmajuk of Stanford (Calif.) University and her associates.

Recent population-based studies have shown consistently low rates of DMARD use, even though evidence-based guidelines recommend early and aggressive treatment.

Dr. Schmajuk and her colleagues assessed medication use in a cohort of 93,143 RA patients enrolled in Medicare managed care plans during a recent 4-year period.

The cohort comprises a nationally representative sample of the managed care population aged 65 years and older.

Overall, 37% of patients were not receiving DMARDs.

These include abatacept, adalimumab, anakinra, azathioprine, cyclophosphamide, cyclosporine, etanercept, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, penicillamine, rituximab, staphylococcal protein A, and sulfasalazine.

In some cases, patients may have declined DMARD treatment, may have had quiescent disease that didn't require treatment, or may have had contraindications to all 17 of these drugs.

The greatest variation in the rate of DMARD use occurred by patient ag.

Only 42% of patients aged 85 years or older received DMARDs, compared with 72%, of those aged 65-69 years.

It is possible that older patients had more comorbidities limiting their ability to use these drugs.

It also is possible that age bias played a role in this result, according to the investigators.

Men had slightly lower rates of use than women, and patients self-identified as black or “other” had lower rates of use (57% and 58%, respectively) than white patients (64%).

The rate of DMARD use was 55% among patients with a low personal income, compared with 64% among those with higher incomes.

Similarly, patients who lived in neighborhoods of low socioeconomic status were less likely to be taking DMARDs than patients living in neighborhoods with higher socioeconomic status.

It is possible that some of these patients don't get DMARDs because they are unable to afford copayments or other forms of cost sharing, the investigators said.

Patients living in the South Atlantic and Middle Atlantic regions of the country had rates of use that were 10% lower than those living in other regions.

The use of DMARDs was 6% lower among patients who were enrolled in for-profit health plans than among those who were enrolled in not-for-profit plans, a difference that was small but statistically significant.

However, variability by health plan was much greater than that statistic alone would convey.

Rates of use of DMARDs varied from a low of 16% in one health plan to a high of 87% in another. This findings held true even after the data had been adjusted to account for differences in case mix.

This finding is “concerning,” Dr. Schmajuk and her associates said (JAMA 2011;305:480-6).

It is unknown whether this 70-point difference in DMARD use is due to differences in the availability or accessibility of specialty care within some health plans or differences in allowances on prescription drug benefits between health plans.

It may even reflect in part inaccurate reporting on the forms used to collect the data, they added.

Whatever the explanations, the large variations in DMARD use are “unacceptable,” the researchers said.

“Targeting educational and quality improvement interventions to patients who are underusing DMARDs and their clinicians will be important to eliminate these disparities,” they said.

Major Finding: The use of disease-modifying antirheumatic drugs varies widely according to patient age, sex, and race; income; location; and health plan.

Data Source: An analysis of Healthcare Effectiveness Data and Information Set data on medication use in a nationally representative sample of 93,134 RA patients enrolled in Medicare managed care plans.

Disclosures: This study was supported by the American College of Rheumatology, National Center for Research Resources, Rosalind Russell Medical Research Centers for Arthritis, National Institutes of Health, State of California Lupus Fund, Arthritis Foundation, Agency for Healthcare Research and Quality, and National Institute of Arthritis and Musculoskeletal and Skin Diseases. An associate of Dr. Schmajuk reported financial ties to Merck and the Pfizer Foundation.

Whether patients with rheumatoid arthritis receive appropriate antirheumatic medications varies widely and depends on their age, sex, race, income, the neighborhood and area of the country where they reside, and their health care plan, judging from recent study findings.

“Although RA was once an inevitably deforming and disabling condition, the development of new DMARDs [disease-modifying antirheumatic drugs] and support for their early use has dramatically improved clinical outcomes for many patients.

“This study suggests that one mechanism for the sociodemographic disparities in RA outcomes in the United States may relate to differences in DMARD receipt,” according to Dr. Gabriela Schmajuk of Stanford (Calif.) University and her associates.

Recent population-based studies have shown consistently low rates of DMARD use, even though evidence-based guidelines recommend early and aggressive treatment.

Dr. Schmajuk and her colleagues assessed medication use in a cohort of 93,143 RA patients enrolled in Medicare managed care plans during a recent 4-year period.

The cohort comprises a nationally representative sample of the managed care population aged 65 years and older.

Overall, 37% of patients were not receiving DMARDs.

These include abatacept, adalimumab, anakinra, azathioprine, cyclophosphamide, cyclosporine, etanercept, gold, hydroxychloroquine, infliximab, leflunomide, methotrexate, minocycline, penicillamine, rituximab, staphylococcal protein A, and sulfasalazine.

In some cases, patients may have declined DMARD treatment, may have had quiescent disease that didn't require treatment, or may have had contraindications to all 17 of these drugs.

The greatest variation in the rate of DMARD use occurred by patient ag.

Only 42% of patients aged 85 years or older received DMARDs, compared with 72%, of those aged 65-69 years.

It is possible that older patients had more comorbidities limiting their ability to use these drugs.

It also is possible that age bias played a role in this result, according to the investigators.

Men had slightly lower rates of use than women, and patients self-identified as black or “other” had lower rates of use (57% and 58%, respectively) than white patients (64%).

The rate of DMARD use was 55% among patients with a low personal income, compared with 64% among those with higher incomes.

Similarly, patients who lived in neighborhoods of low socioeconomic status were less likely to be taking DMARDs than patients living in neighborhoods with higher socioeconomic status.

It is possible that some of these patients don't get DMARDs because they are unable to afford copayments or other forms of cost sharing, the investigators said.

Patients living in the South Atlantic and Middle Atlantic regions of the country had rates of use that were 10% lower than those living in other regions.

The use of DMARDs was 6% lower among patients who were enrolled in for-profit health plans than among those who were enrolled in not-for-profit plans, a difference that was small but statistically significant.

However, variability by health plan was much greater than that statistic alone would convey.

Rates of use of DMARDs varied from a low of 16% in one health plan to a high of 87% in another. This findings held true even after the data had been adjusted to account for differences in case mix.

This finding is “concerning,” Dr. Schmajuk and her associates said (JAMA 2011;305:480-6).

It is unknown whether this 70-point difference in DMARD use is due to differences in the availability or accessibility of specialty care within some health plans or differences in allowances on prescription drug benefits between health plans.

It may even reflect in part inaccurate reporting on the forms used to collect the data, they added.

Whatever the explanations, the large variations in DMARD use are “unacceptable,” the researchers said.

“Targeting educational and quality improvement interventions to patients who are underusing DMARDs and their clinicians will be important to eliminate these disparities,” they said.

The American College of Rheumatology and the European League Against Rheumatism have issued two new provisional definitions for remission in rheumatoid arthritis for clinical trials.

The need for two definitions was based on considerations of both face and predictive validity, the need for stringency, and the determination by a 27-member committee that patient-reported outcomes should be among the criteria, reported lead author Dr. David T. Felson, professor of medicine and epidemiology at Boston University, and his coauthors (Ann. Rheum. Dis. 2011;70:404-13).

One definition requires the patient to satisfy all of the following at any time point: no more than one tender or swollen joint, C-reactive protein of less than or equal to 1 mg/dL, and a patient global assessment of 1 or less on a 0- to 10-point scale. For the tender and swollen joint counts, it is preferable to include feet and ankles in addition to the standard 28-joint count.

The second definition is based on a composite index of RA activity, the Simplified Disease Activity Index (SDAI) score, which is the sum of the tender and swollen joint count (using 28 joints), patient global assessment (0-10 scale), physician global assessment (0-10 scale), and C-reactive protein level (mg/dL). At any time point, the patient must have an SDAI score of 3.3 or less to be considered to be in remission.

The authors recommend that one of the two definitions be selected as a trial outcome measure but that the results of both be reported.

The criteria have been approved provisionally by both ACR and EULAR, meaning that they have been quantitatively validated using patient data but have not undergone validation based on an external data set. As such, they are expected to undergo intermittent updates.

The previous ACR definition of remission in RA was developed in 1981, prior to the introduction of the RA core set measures and before the advent of biologics for treatment, when true remission was rare.

In an accompanying editorial, Dr. Lennart T.H. Jacobsson and Dr. Merete Lund Hetland said the new criteria represent a step forward (Ann. Rheum. Dis. 2011;70:401-3) 2

“The old remission criteria were like silent films – with disease potentially progressing silently under a cover of remission that allowed substantial disease activity to be present. The new criteria are more like a 3-D movie, requiring no or minimal activity based on three dimensions: clinician's (swollen and tender joint counts) and patient's (global health score) judgments together with laboratory data (CRP).”

The ACR/EULAR authors noted that because the definitions have not yet been validated in observational data sets – that's the next step – their uses in clinical practice settings are limited.

The document provides additional definitions including joint counts and physican/observer/patient global assessments that do not require an acute-phase reactant (such as C-reactive protein) and therefore may be more useful in clinical settings.

“Nevertheless, our preliminary suggestions for defining remission in clinical practice are still incomplete, as we did not test them in a clinic-based setting.” Inclusion of acute-phase reactants is important because they predict later radiographic damage, they noted.

However, the editorialists Dr. Jacobsson and Dr. Hetland noted that the criteria are feasible to use in routine care, and they can assist in the monitoring of treated patients.

Moreover, the generalizability of the criteria is likely to be improved by the use of contemporary data from clinical trials published during the last decade in which modern biological therapy has been represented in one or more treatment arms.

The new definitions also “represent another successful ACR-EULAR collaboration,” said Dr. Jacobsson, professor of clinical sciences (rheumatology) at Lund University, Malmo, Sweden, and Dr. Hetland, of Copenhagen University Hospital, Glostrup, Denmark.

And, they added, “With 'treat to target' as the modern treatment principle, permanent remission is the ultimate goal – although not a realistic one in all patients. Nevertheless, aiming at remission will also improve outcome in those patients who do not achieve remission.”

They noted that subsequent additions of additional response criteria such as imaging techniques will probably render the definitions more complex and less suitable for use in clinical practice.

“The new preliminary ACR/EULAR criteria are therefore likely to be used for a long time.”

The project was funded by the ACR, EULAR, and a grant from the National Institutes of Health. Dr. Felson, Dr. Jacobsson, and Dr. Hetland all stated that they had no disclosures.

The American College of Rheumatology and the European League Against Rheumatism have issued two new provisional definitions for remission in rheumatoid arthritis for clinical trials.

The need for two definitions was based on considerations of both face and predictive validity, the need for stringency, and the determination by a 27-member committee that patient-reported outcomes should be among the criteria, reported lead author Dr. David T. Felson, professor of medicine and epidemiology at Boston University, and his coauthors (Ann. Rheum. Dis. 2011;70:404-13).

One definition requires the patient to satisfy all of the following at any time point: no more than one tender or swollen joint, C-reactive protein of less than or equal to 1 mg/dL, and a patient global assessment of 1 or less on a 0- to 10-point scale. For the tender and swollen joint counts, it is preferable to include feet and ankles in addition to the standard 28-joint count.

The second definition is based on a composite index of RA activity, the Simplified Disease Activity Index (SDAI) score, which is the sum of the tender and swollen joint count (using 28 joints), patient global assessment (0-10 scale), physician global assessment (0-10 scale), and C-reactive protein level (mg/dL). At any time point, the patient must have an SDAI score of 3.3 or less to be considered to be in remission.

The authors recommend that one of the two definitions be selected as a trial outcome measure but that the results of both be reported.

The criteria have been approved provisionally by both ACR and EULAR, meaning that they have been quantitatively validated using patient data but have not undergone validation based on an external data set. As such, they are expected to undergo intermittent updates.

The previous ACR definition of remission in RA was developed in 1981, prior to the introduction of the RA core set measures and before the advent of biologics for treatment, when true remission was rare.

In an accompanying editorial, Dr. Lennart T.H. Jacobsson and Dr. Merete Lund Hetland said the new criteria represent a step forward (Ann. Rheum. Dis. 2011;70:401-3) 2

“The old remission criteria were like silent films – with disease potentially progressing silently under a cover of remission that allowed substantial disease activity to be present. The new criteria are more like a 3-D movie, requiring no or minimal activity based on three dimensions: clinician's (swollen and tender joint counts) and patient's (global health score) judgments together with laboratory data (CRP).”

The ACR/EULAR authors noted that because the definitions have not yet been validated in observational data sets – that's the next step – their uses in clinical practice settings are limited.

The document provides additional definitions including joint counts and physican/observer/patient global assessments that do not require an acute-phase reactant (such as C-reactive protein) and therefore may be more useful in clinical settings.

“Nevertheless, our preliminary suggestions for defining remission in clinical practice are still incomplete, as we did not test them in a clinic-based setting.” Inclusion of acute-phase reactants is important because they predict later radiographic damage, they noted.

However, the editorialists Dr. Jacobsson and Dr. Hetland noted that the criteria are feasible to use in routine care, and they can assist in the monitoring of treated patients.

Moreover, the generalizability of the criteria is likely to be improved by the use of contemporary data from clinical trials published during the last decade in which modern biological therapy has been represented in one or more treatment arms.

The new definitions also “represent another successful ACR-EULAR collaboration,” said Dr. Jacobsson, professor of clinical sciences (rheumatology) at Lund University, Malmo, Sweden, and Dr. Hetland, of Copenhagen University Hospital, Glostrup, Denmark.

And, they added, “With 'treat to target' as the modern treatment principle, permanent remission is the ultimate goal – although not a realistic one in all patients. Nevertheless, aiming at remission will also improve outcome in those patients who do not achieve remission.”

They noted that subsequent additions of additional response criteria such as imaging techniques will probably render the definitions more complex and less suitable for use in clinical practice.

“The new preliminary ACR/EULAR criteria are therefore likely to be used for a long time.”

The project was funded by the ACR, EULAR, and a grant from the National Institutes of Health. Dr. Felson, Dr. Jacobsson, and Dr. Hetland all stated that they had no disclosures.

The American College of Rheumatology and the European League Against Rheumatism have issued two new provisional definitions for remission in rheumatoid arthritis for clinical trials.

The need for two definitions was based on considerations of both face and predictive validity, the need for stringency, and the determination by a 27-member committee that patient-reported outcomes should be among the criteria, reported lead author Dr. David T. Felson, professor of medicine and epidemiology at Boston University, and his coauthors (Ann. Rheum. Dis. 2011;70:404-13).

One definition requires the patient to satisfy all of the following at any time point: no more than one tender or swollen joint, C-reactive protein of less than or equal to 1 mg/dL, and a patient global assessment of 1 or less on a 0- to 10-point scale. For the tender and swollen joint counts, it is preferable to include feet and ankles in addition to the standard 28-joint count.

The second definition is based on a composite index of RA activity, the Simplified Disease Activity Index (SDAI) score, which is the sum of the tender and swollen joint count (using 28 joints), patient global assessment (0-10 scale), physician global assessment (0-10 scale), and C-reactive protein level (mg/dL). At any time point, the patient must have an SDAI score of 3.3 or less to be considered to be in remission.

The authors recommend that one of the two definitions be selected as a trial outcome measure but that the results of both be reported.

The criteria have been approved provisionally by both ACR and EULAR, meaning that they have been quantitatively validated using patient data but have not undergone validation based on an external data set. As such, they are expected to undergo intermittent updates.

The previous ACR definition of remission in RA was developed in 1981, prior to the introduction of the RA core set measures and before the advent of biologics for treatment, when true remission was rare.

In an accompanying editorial, Dr. Lennart T.H. Jacobsson and Dr. Merete Lund Hetland said the new criteria represent a step forward (Ann. Rheum. Dis. 2011;70:401-3) 2

“The old remission criteria were like silent films – with disease potentially progressing silently under a cover of remission that allowed substantial disease activity to be present. The new criteria are more like a 3-D movie, requiring no or minimal activity based on three dimensions: clinician's (swollen and tender joint counts) and patient's (global health score) judgments together with laboratory data (CRP).”

The ACR/EULAR authors noted that because the definitions have not yet been validated in observational data sets – that's the next step – their uses in clinical practice settings are limited.

The document provides additional definitions including joint counts and physican/observer/patient global assessments that do not require an acute-phase reactant (such as C-reactive protein) and therefore may be more useful in clinical settings.

“Nevertheless, our preliminary suggestions for defining remission in clinical practice are still incomplete, as we did not test them in a clinic-based setting.” Inclusion of acute-phase reactants is important because they predict later radiographic damage, they noted.

However, the editorialists Dr. Jacobsson and Dr. Hetland noted that the criteria are feasible to use in routine care, and they can assist in the monitoring of treated patients.

Moreover, the generalizability of the criteria is likely to be improved by the use of contemporary data from clinical trials published during the last decade in which modern biological therapy has been represented in one or more treatment arms.

The new definitions also “represent another successful ACR-EULAR collaboration,” said Dr. Jacobsson, professor of clinical sciences (rheumatology) at Lund University, Malmo, Sweden, and Dr. Hetland, of Copenhagen University Hospital, Glostrup, Denmark.

And, they added, “With 'treat to target' as the modern treatment principle, permanent remission is the ultimate goal – although not a realistic one in all patients. Nevertheless, aiming at remission will also improve outcome in those patients who do not achieve remission.”

They noted that subsequent additions of additional response criteria such as imaging techniques will probably render the definitions more complex and less suitable for use in clinical practice.

“The new preliminary ACR/EULAR criteria are therefore likely to be used for a long time.”

The project was funded by the ACR, EULAR, and a grant from the National Institutes of Health. Dr. Felson, Dr. Jacobsson, and Dr. Hetland all stated that they had no disclosures.

Inactivated flu vaccine is an option for patients with autoimmune inflammatory rheumatic diseases, but any vaccination for these patients should occur during periods of stable disease, according to new recommendations from the European League Against Rheumatism.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for infections, but vaccination can cause flares of the disease, wrote Dr. Sander van Assen of the University Medical Center Groningen (the Netherlands), and colleagues. To help rheumatologists make informed decisions about patient vaccinations, EULAR convened a task force that developed eight key questions and 13 evidence-based recommendations (Ann. Rheum. Dis. 2011;70:414-22).

"For the most part, such recommendations have been lacking and the field has been changing very quickly as new drugs are developed and roll into the marketplace," according to infectious disease specialist Dr. Kevin Winthrop of the Oregon Health and Science University in Portland. "New drugs and new vaccines make these recommendations a moving target, and it was extremely important for the expert group to sit down, review the latest data, and codify their thoughts. For the most part, there is a lack of data regarding the efficacy and utility of many of these vaccines in these patients, and it is often unclear how their immunosuppressive medications and underlying diseases affect vaccine responsiveness. With certain biologics, we know that some vaccines are diminished in their immunogenicity and it is important to clarify for physicians when these vaccines can and should be given," he said.

The following were the committee’s questions:

• Is the risk of infections for which vaccines are available increased in patients with AIIRD in general, and specifically in those with active disease and in those using immunomodulation agents?

• Do vaccines decrease the risk of infections in patients with AIIRD in general, and specifically in those with unstable disease and in those using immunomodulating agents?

• Do vaccines cause significant harm in patients with AIIRD in general, and specifically in those with unstable disease or in those using immunomodulating agents?

• Does the timing of vaccination in relation to disease activity and treatment with immunomodulating agents affect important harms of vaccination in patients with AIIRD?

• Does the timing of vaccination in relation to disease activity and treatment with immunomodulating agents affect the effectiveness of vaccination in patients with AIIRD?

• Does revaccination with any vaccines increase the effectiveness in patients with AIIRD?

• Does revaccination with any vaccine increase significant harms in patients with AIIRD?

• Is vaccination in patients with AIIRD cost effective?

The expert committee members represented 11 European countries. They reviewed studies from 1966 through October 2009, as well as abstracts presented at EULAR in 2008 and 2009 and at the American College of Rheumatology annual meeting in 2007 and 2008.

Their evidence-based recommendations for vaccination in patients with AIIRDs were the following:

• Assess vaccination status of an AIIRD patient at an initial work-up.

• Vaccinate patients during times of stable disease whenever possible.

• Avoid live, attenuated vaccines whenever possible in immunosuppressed patients.

• Vaccinate patients before starting B-cell–depleting biologic therapy if possible, but vaccines can be given during the use of disease-modifying antirheumatic drugs and tumor necrosis factor–alpha–blocking agents.

• Strongly consider inactivated flu vaccine for patients with AIIRD.

• Strongly consider PPV23 (23-valent pneumococcal polysaccharide vaccination) for AIIRD patients.

• Vaccinate AIIRD patients for tetanus toxoid in accordance with recommendations for the general population.

• Consider herpes zoster vaccination in AIIRD patients.

• Consider human papillomavirus vaccination for selected patients with AIIRD (young women with systemic lupus erythematosus up to age 25 years).

• Vaccinate hyposplenic or asplenic patients with AIIRD with vaccines for influenza, pneumococcal, Haemophilus influenzae type b, and meningococcal C.

• Vaccinate only at-risk AIIRD patients for hepatitis A and/or B.

• Vaccinate traveling AIIRD patients according to the general rules for travelers, but avoid live, attenuated vaccines whenever possible in immunosuppressed patients.

• Do not vaccinate AIIRD patients with the BCG vaccine for tuberculosis.

"The exact implementation of the current recommendations may need to take into account local differences in specific countries and settings," the researchers noted. They added that more research is needed to continue to assess the effects of vaccination in AIIRDs patients.

In an interview, Dr. Winthrop noted that the "EULAR statement includes a thoughtful discussion of needed research. Clearly, we need better information regarding the risk of vaccine-preventable diseases in this population, as well as the outcomes of such infections and how these outcomes are modulated by certain immunosuppressive therapies. Such research would help better clarify the potential benefits of vaccination. On the adverse event side, further research is certainly necessary to better understand the risk of such vaccines (particularly live vaccines) and how that risk is modulated by immunosuppressive therapies, most notably biologic therapies. Lastly, studies evaluating the safety and efficacy of new vaccines [such as zoster vaccine and the new conjugated pneumococcal vaccine PCV13] in the context of existing and new biologic therapies remains an important area of study."

The study was funded by the European League Against Rheumatism. The researchers had no financial conflicts to disclose. Dr. Winthrop said he had no disclosures.

Inactivated flu vaccine is an option for patients with autoimmune inflammatory rheumatic diseases, but any vaccination for these patients should occur during periods of stable disease, according to new recommendations from the European League Against Rheumatism.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for infections, but vaccination can cause flares of the disease, wrote Dr. Sander van Assen of the University Medical Center Groningen (the Netherlands), and colleagues. To help rheumatologists make informed decisions about patient vaccinations, EULAR convened a task force that developed eight key questions and 13 evidence-based recommendations (Ann. Rheum. Dis. 2011;70:414-22).

"For the most part, such recommendations have been lacking and the field has been changing very quickly as new drugs are developed and roll into the marketplace," according to infectious disease specialist Dr. Kevin Winthrop of the Oregon Health and Science University in Portland. "New drugs and new vaccines make these recommendations a moving target, and it was extremely important for the expert group to sit down, review the latest data, and codify their thoughts. For the most part, there is a lack of data regarding the efficacy and utility of many of these vaccines in these patients, and it is often unclear how their immunosuppressive medications and underlying diseases affect vaccine responsiveness. With certain biologics, we know that some vaccines are diminished in their immunogenicity and it is important to clarify for physicians when these vaccines can and should be given," he said.

The following were the committee’s questions:

• Is the risk of infections for which vaccines are available increased in patients with AIIRD in general, and specifically in those with active disease and in those using immunomodulation agents?

• Do vaccines decrease the risk of infections in patients with AIIRD in general, and specifically in those with unstable disease and in those using immunomodulating agents?

• Do vaccines cause significant harm in patients with AIIRD in general, and specifically in those with unstable disease or in those using immunomodulating agents?

• Does the timing of vaccination in relation to disease activity and treatment with immunomodulating agents affect important harms of vaccination in patients with AIIRD?

• Does the timing of vaccination in relation to disease activity and treatment with immunomodulating agents affect the effectiveness of vaccination in patients with AIIRD?

• Does revaccination with any vaccines increase the effectiveness in patients with AIIRD?

• Does revaccination with any vaccine increase significant harms in patients with AIIRD?

• Is vaccination in patients with AIIRD cost effective?

The expert committee members represented 11 European countries. They reviewed studies from 1966 through October 2009, as well as abstracts presented at EULAR in 2008 and 2009 and at the American College of Rheumatology annual meeting in 2007 and 2008.

Their evidence-based recommendations for vaccination in patients with AIIRDs were the following:

• Assess vaccination status of an AIIRD patient at an initial work-up.

• Vaccinate patients during times of stable disease whenever possible.

• Avoid live, attenuated vaccines whenever possible in immunosuppressed patients.

• Vaccinate patients before starting B-cell–depleting biologic therapy if possible, but vaccines can be given during the use of disease-modifying antirheumatic drugs and tumor necrosis factor–alpha–blocking agents.

• Strongly consider inactivated flu vaccine for patients with AIIRD.

• Strongly consider PPV23 (23-valent pneumococcal polysaccharide vaccination) for AIIRD patients.

• Vaccinate AIIRD patients for tetanus toxoid in accordance with recommendations for the general population.

• Consider herpes zoster vaccination in AIIRD patients.

• Consider human papillomavirus vaccination for selected patients with AIIRD (young women with systemic lupus erythematosus up to age 25 years).

• Vaccinate hyposplenic or asplenic patients with AIIRD with vaccines for influenza, pneumococcal, Haemophilus influenzae type b, and meningococcal C.

• Vaccinate only at-risk AIIRD patients for hepatitis A and/or B.

• Vaccinate traveling AIIRD patients according to the general rules for travelers, but avoid live, attenuated vaccines whenever possible in immunosuppressed patients.

• Do not vaccinate AIIRD patients with the BCG vaccine for tuberculosis.

"The exact implementation of the current recommendations may need to take into account local differences in specific countries and settings," the researchers noted. They added that more research is needed to continue to assess the effects of vaccination in AIIRDs patients.

In an interview, Dr. Winthrop noted that the "EULAR statement includes a thoughtful discussion of needed research. Clearly, we need better information regarding the risk of vaccine-preventable diseases in this population, as well as the outcomes of such infections and how these outcomes are modulated by certain immunosuppressive therapies. Such research would help better clarify the potential benefits of vaccination. On the adverse event side, further research is certainly necessary to better understand the risk of such vaccines (particularly live vaccines) and how that risk is modulated by immunosuppressive therapies, most notably biologic therapies. Lastly, studies evaluating the safety and efficacy of new vaccines [such as zoster vaccine and the new conjugated pneumococcal vaccine PCV13] in the context of existing and new biologic therapies remains an important area of study."

The study was funded by the European League Against Rheumatism. The researchers had no financial conflicts to disclose. Dr. Winthrop said he had no disclosures.

Inactivated flu vaccine is an option for patients with autoimmune inflammatory rheumatic diseases, but any vaccination for these patients should occur during periods of stable disease, according to new recommendations from the European League Against Rheumatism.

Patients with autoimmune inflammatory rheumatic diseases (AIIRDs) are at increased risk for infections, but vaccination can cause flares of the disease, wrote Dr. Sander van Assen of the University Medical Center Groningen (the Netherlands), and colleagues. To help rheumatologists make informed decisions about patient vaccinations, EULAR convened a task force that developed eight key questions and 13 evidence-based recommendations (Ann. Rheum. Dis. 2011;70:414-22).

"For the most part, such recommendations have been lacking and the field has been changing very quickly as new drugs are developed and roll into the marketplace," according to infectious disease specialist Dr. Kevin Winthrop of the Oregon Health and Science University in Portland. "New drugs and new vaccines make these recommendations a moving target, and it was extremely important for the expert group to sit down, review the latest data, and codify their thoughts. For the most part, there is a lack of data regarding the efficacy and utility of many of these vaccines in these patients, and it is often unclear how their immunosuppressive medications and underlying diseases affect vaccine responsiveness. With certain biologics, we know that some vaccines are diminished in their immunogenicity and it is important to clarify for physicians when these vaccines can and should be given," he said.

The following were the committee’s questions:

• Is the risk of infections for which vaccines are available increased in patients with AIIRD in general, and specifically in those with active disease and in those using immunomodulation agents?

• Do vaccines decrease the risk of infections in patients with AIIRD in general, and specifically in those with unstable disease and in those using immunomodulating agents?

• Do vaccines cause significant harm in patients with AIIRD in general, and specifically in those with unstable disease or in those using immunomodulating agents?

• Does the timing of vaccination in relation to disease activity and treatment with immunomodulating agents affect important harms of vaccination in patients with AIIRD?

• Does the timing of vaccination in relation to disease activity and treatment with immunomodulating agents affect the effectiveness of vaccination in patients with AIIRD?

• Does revaccination with any vaccines increase the effectiveness in patients with AIIRD?

• Does revaccination with any vaccine increase significant harms in patients with AIIRD?

• Is vaccination in patients with AIIRD cost effective?

The expert committee members represented 11 European countries. They reviewed studies from 1966 through October 2009, as well as abstracts presented at EULAR in 2008 and 2009 and at the American College of Rheumatology annual meeting in 2007 and 2008.

Their evidence-based recommendations for vaccination in patients with AIIRDs were the following:

• Assess vaccination status of an AIIRD patient at an initial work-up.

• Vaccinate patients during times of stable disease whenever possible.

• Avoid live, attenuated vaccines whenever possible in immunosuppressed patients.

• Vaccinate patients before starting B-cell–depleting biologic therapy if possible, but vaccines can be given during the use of disease-modifying antirheumatic drugs and tumor necrosis factor–alpha–blocking agents.

• Strongly consider inactivated flu vaccine for patients with AIIRD.

• Strongly consider PPV23 (23-valent pneumococcal polysaccharide vaccination) for AIIRD patients.

• Vaccinate AIIRD patients for tetanus toxoid in accordance with recommendations for the general population.

• Consider herpes zoster vaccination in AIIRD patients.

• Consider human papillomavirus vaccination for selected patients with AIIRD (young women with systemic lupus erythematosus up to age 25 years).

• Vaccinate hyposplenic or asplenic patients with AIIRD with vaccines for influenza, pneumococcal, Haemophilus influenzae type b, and meningococcal C.

• Vaccinate only at-risk AIIRD patients for hepatitis A and/or B.

• Vaccinate traveling AIIRD patients according to the general rules for travelers, but avoid live, attenuated vaccines whenever possible in immunosuppressed patients.

• Do not vaccinate AIIRD patients with the BCG vaccine for tuberculosis.

"The exact implementation of the current recommendations may need to take into account local differences in specific countries and settings," the researchers noted. They added that more research is needed to continue to assess the effects of vaccination in AIIRDs patients.

In an interview, Dr. Winthrop noted that the "EULAR statement includes a thoughtful discussion of needed research. Clearly, we need better information regarding the risk of vaccine-preventable diseases in this population, as well as the outcomes of such infections and how these outcomes are modulated by certain immunosuppressive therapies. Such research would help better clarify the potential benefits of vaccination. On the adverse event side, further research is certainly necessary to better understand the risk of such vaccines (particularly live vaccines) and how that risk is modulated by immunosuppressive therapies, most notably biologic therapies. Lastly, studies evaluating the safety and efficacy of new vaccines [such as zoster vaccine and the new conjugated pneumococcal vaccine PCV13] in the context of existing and new biologic therapies remains an important area of study."

The study was funded by the European League Against Rheumatism. The researchers had no financial conflicts to disclose. Dr. Winthrop said he had no disclosures.

ORLANDO — Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.

Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a significant difference, Gary E. Raskob, Ph.D., said.

Prevention of major venous thromboembolism is “a significant issue in health care in the United States,” where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City. To provide more precise estimates of the incidence of major VTE and safety outcomes, the researchers combined data from two phase III, randomized, double-blind trials of patients who had undergone knee (ADVANCE-2 study) or hip (ADVANCE-3) replacement. A total of 8,464 were randomized to apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).

Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), vs. 51 patients in the enoxaparin group (1.50%).

Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group.

Dr. Raskob has financial relationships with Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.

To see an interview with Dr. Gary E. Raskob, go to

Source Heidi Splete/Elsevier Global Medical Newswww.rheumatologynews.com

ORLANDO — Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.

Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a significant difference, Gary E. Raskob, Ph.D., said.

Prevention of major venous thromboembolism is “a significant issue in health care in the United States,” where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City. To provide more precise estimates of the incidence of major VTE and safety outcomes, the researchers combined data from two phase III, randomized, double-blind trials of patients who had undergone knee (ADVANCE-2 study) or hip (ADVANCE-3) replacement. A total of 8,464 were randomized to apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).

Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), vs. 51 patients in the enoxaparin group (1.50%).

Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group.

Dr. Raskob has financial relationships with Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.

To see an interview with Dr. Gary E. Raskob, go to

Source Heidi Splete/Elsevier Global Medical Newswww.rheumatologynews.com

ORLANDO — Oral apixaban reduced the incidence of major venous thromboembolism after joint replacement surgery by approximately half compared with enoxaparin, with no increased risk of bleeding, investigators have reported.

Of approximately 7,000 patients who underwent thromboprophylaxis after surgery, major VTE occurred in 0.68% of those who had received apixaban, compared with 1.50% who had been given enoxaparin. This was a significant difference, Gary E. Raskob, Ph.D., said.

Prevention of major venous thromboembolism is “a significant issue in health care in the United States,” where the number of knee and hip replacements is expected to increase, said Dr. Raskob, dean of the College of Public Health at the University of Oklahoma Health Sciences Center in Oklahoma City. To provide more precise estimates of the incidence of major VTE and safety outcomes, the researchers combined data from two phase III, randomized, double-blind trials of patients who had undergone knee (ADVANCE-2 study) or hip (ADVANCE-3) replacement. A total of 8,464 were randomized to apixaban, a novel orally administered factor Xa inhibitor (4,236 patients), or enoxaparin (4,228 patients).

Efficacy results related to VTE were based on 3,394 patients in each group. Major VTE occurred in 23 patients in the apixaban group (0.68%), vs. 51 patients in the enoxaparin group (1.50%).

Bleeding results were based on 4,174 apixaban patients and 4,228 enoxaparin patients. Major bleeding occurred in 31 patients in the apixaban group and 32 in the enoxaparin group (0.74% vs. 0.77%). Major bleeding at the surgical site occurred in 26 in the apixaban group and 27 in the enoxaparin group.

Dr. Raskob has financial relationships with Bristol-Meyers Squibb, Pfizer, Bayer, Johnson & Johnson, Sanofi Aventis, and Daiichi Sankyo.

To see an interview with Dr. Gary E. Raskob, go to

Source Heidi Splete/Elsevier Global Medical Newswww.rheumatologynews.com

In obese patients with knee osteoarthritis, significant weight loss after bariatric surgery reduced pain and stiffness, decreased low-grade inflammation, and changed cartilage turnover, according to a study published in the journal.

In addition to the well-known relationship between obesity and onset of knee osteoarthritis (OA), several studies have now shown that the association goes beyond the increase in mechanical load on the tibiofemoral cartilage. “Adipose tissue may act as an endocrine organ, releasing several proinflammatory mediators and adipokines in blood that may participate in cartilage alteration in obese patients,” according to Dr. Pascal Richette of Hôpital Lariboisière and coauthors. The authors added, “Trials that have assessed the efficacy of surgically induced massive weight loss on knee OA symptoms are scarce and have not specifically included patients with well-defined radiographic evidence of knee OA, as in our study” (Ann. Rheum. Dis. 2011;70:139-44).

The authors studied 44 obese patients (36 women) with a baseline body mass index of 50.7 before surgery and moderate to severe knee OA. The patients underwent laparoscopic Roux-en-Y gastric bypass surgery or laparoscopic adjustable gastric banding. Patient data were collected before and 6 months after the surgery. At 6 months, patients had a 20% drop from baseline BMIs. Their VAS (visual acuity scores) decreased from 50 mm to 24.5 mm and their scores on the WOMAC (Western Ontario MacMaster) Questionnaire improved.

Significant decreases were seen in average serum levels of interleukin-6 (IL-6), which declined by 26%, and of high-sensitivity C-reactive protein (hsCRP), which dropped 46%. Also, weight loss was associated with changes in adipokine levels: Mean serum leptin concentration was decreased by 48% and serum level of adiponectin was increased by 21%, the authors reported.

The average serum level of procollagen type II N-terminal propeptide (PIIANP), a marker of cartilage synthesis, rose 32%, while the serum level of cartilage oligomeric matrix protein (COMP) decreased by 36%. “These results are the first to suggest a benefit of weight loss on both cartilage anabolism and catabolism,” the authors wrote.

The researchers found a significant correlation between IL-6 level and WOMAC Questionnaire scores as well as between urinary type II collagen helical peptide (helix-II) and hsCRP. Variation in COMP concentration was significantly correlated with changes in VAS pain scores and WOMAC stiffness score, the authors wrote, adding, “Our findings extend the results of recent work showing a significant association of IL-6 circulating levels and the prevalence and incidence of knee OA.”

In obese patients with knee osteoarthritis, significant weight loss after bariatric surgery reduced pain and stiffness, decreased low-grade inflammation, and changed cartilage turnover, according to a study published in the journal.

In addition to the well-known relationship between obesity and onset of knee osteoarthritis (OA), several studies have now shown that the association goes beyond the increase in mechanical load on the tibiofemoral cartilage. “Adipose tissue may act as an endocrine organ, releasing several proinflammatory mediators and adipokines in blood that may participate in cartilage alteration in obese patients,” according to Dr. Pascal Richette of Hôpital Lariboisière and coauthors. The authors added, “Trials that have assessed the efficacy of surgically induced massive weight loss on knee OA symptoms are scarce and have not specifically included patients with well-defined radiographic evidence of knee OA, as in our study” (Ann. Rheum. Dis. 2011;70:139-44).

The authors studied 44 obese patients (36 women) with a baseline body mass index of 50.7 before surgery and moderate to severe knee OA. The patients underwent laparoscopic Roux-en-Y gastric bypass surgery or laparoscopic adjustable gastric banding. Patient data were collected before and 6 months after the surgery. At 6 months, patients had a 20% drop from baseline BMIs. Their VAS (visual acuity scores) decreased from 50 mm to 24.5 mm and their scores on the WOMAC (Western Ontario MacMaster) Questionnaire improved.

Significant decreases were seen in average serum levels of interleukin-6 (IL-6), which declined by 26%, and of high-sensitivity C-reactive protein (hsCRP), which dropped 46%. Also, weight loss was associated with changes in adipokine levels: Mean serum leptin concentration was decreased by 48% and serum level of adiponectin was increased by 21%, the authors reported.

The average serum level of procollagen type II N-terminal propeptide (PIIANP), a marker of cartilage synthesis, rose 32%, while the serum level of cartilage oligomeric matrix protein (COMP) decreased by 36%. “These results are the first to suggest a benefit of weight loss on both cartilage anabolism and catabolism,” the authors wrote.

The researchers found a significant correlation between IL-6 level and WOMAC Questionnaire scores as well as between urinary type II collagen helical peptide (helix-II) and hsCRP. Variation in COMP concentration was significantly correlated with changes in VAS pain scores and WOMAC stiffness score, the authors wrote, adding, “Our findings extend the results of recent work showing a significant association of IL-6 circulating levels and the prevalence and incidence of knee OA.”

In obese patients with knee osteoarthritis, significant weight loss after bariatric surgery reduced pain and stiffness, decreased low-grade inflammation, and changed cartilage turnover, according to a study published in the journal.

In addition to the well-known relationship between obesity and onset of knee osteoarthritis (OA), several studies have now shown that the association goes beyond the increase in mechanical load on the tibiofemoral cartilage. “Adipose tissue may act as an endocrine organ, releasing several proinflammatory mediators and adipokines in blood that may participate in cartilage alteration in obese patients,” according to Dr. Pascal Richette of Hôpital Lariboisière and coauthors. The authors added, “Trials that have assessed the efficacy of surgically induced massive weight loss on knee OA symptoms are scarce and have not specifically included patients with well-defined radiographic evidence of knee OA, as in our study” (Ann. Rheum. Dis. 2011;70:139-44).

The authors studied 44 obese patients (36 women) with a baseline body mass index of 50.7 before surgery and moderate to severe knee OA. The patients underwent laparoscopic Roux-en-Y gastric bypass surgery or laparoscopic adjustable gastric banding. Patient data were collected before and 6 months after the surgery. At 6 months, patients had a 20% drop from baseline BMIs. Their VAS (visual acuity scores) decreased from 50 mm to 24.5 mm and their scores on the WOMAC (Western Ontario MacMaster) Questionnaire improved.

Significant decreases were seen in average serum levels of interleukin-6 (IL-6), which declined by 26%, and of high-sensitivity C-reactive protein (hsCRP), which dropped 46%. Also, weight loss was associated with changes in adipokine levels: Mean serum leptin concentration was decreased by 48% and serum level of adiponectin was increased by 21%, the authors reported.

The average serum level of procollagen type II N-terminal propeptide (PIIANP), a marker of cartilage synthesis, rose 32%, while the serum level of cartilage oligomeric matrix protein (COMP) decreased by 36%. “These results are the first to suggest a benefit of weight loss on both cartilage anabolism and catabolism,” the authors wrote.

The researchers found a significant correlation between IL-6 level and WOMAC Questionnaire scores as well as between urinary type II collagen helical peptide (helix-II) and hsCRP. Variation in COMP concentration was significantly correlated with changes in VAS pain scores and WOMAC stiffness score, the authors wrote, adding, “Our findings extend the results of recent work showing a significant association of IL-6 circulating levels and the prevalence and incidence of knee OA.”

New recommendations from the European League Against Rheumatism provide structure to the growing practice of including patient representatives in research projects.

The recommendations should be useful not only within the European League Against Rheumatism (EULAR) but also to other medical researchers, Maarten P. T. de Wit of Vrije Universiteit Medical Centre, Amsterdam, and his associates reported. EULAR convened a 16-member task force that crafted eight recommendations to promote inclusion of the patient perspective in EULAR-funded scientific research (Ann. Rheum. Dis. 2011[doi:10.1136/ard.2010.135129]).

Some previous reports suggest that the benefits of including patient representatives in research outweigh the drawbacks. Although including one or more patient representatives has become “usual practice” in EULAR scientific projects, the League's standardized procedures previously have not described how best to do this, the task force said.

They defined patient research partners as “persons with a relevant disease who operate as active research team members on an equal basis with professional researchers, adding the benefit of their experiential knowledge to any phase of the project.” Including patient research partners can help prevent mismatches between patient preferences and the focus of research, lead to more patient-oriented research agendas, empower patients, and build trust between patient organizations and medical institutions, data suggest.

The task force of three rheumatologists, one rheumatologist/epidemiologist, two allied health professionals, two research organization representatives, and eight patient research partners from six countries reviewed the literature and met twice to develop the recommendations, which were then evaluated by 28 patient representatives and 53 health professionals.

First, the task force urged that clinical researchers and groups work with patient research partners when developing guidelines or recommendations, and that other researchers consider patient participation. Patients' experiential knowledge is important even for laboratory-based research, and researchers who do not include patient partners should justify that decision, they said.

Second, patient participation should be considered for all phases of a research project and is essential in the early stages of research when critical decisions about the protocol and project are made. If this recommendation is not followed, investigators should explain why when publishing results.

Third, each project should include at least two patient research partners. There's no solid evidence to support this, but it adds to the team's diversity and supports the patient partners, and provides a substitute if one patient is absent due to rheumatic illness. This recommendation also drew more support from patients in the group of experts, winning agreement from 26 patients (93%) compared with 36 professionals (68%).

Fourth, give potential patient research partners a clear description of the minimum requirements for the position and clarify the roles of the patient partners and the principal investigator.

Fifth, take into account the patient's communication skills, motivation, and attitude when selecting patient research partners. Having a critical but constructive and proactive attitude is ideal. Academic training is not necessary and a medical background might even be undesirable, though some familiarity with medical terminology helps. “Thinking like an outsider is crucial to provide experiential knowledge,” the task force said.

Sixth, a good attitude, good communication, and good support from the principal investigator are crucial for the full participation of patient partners. These skills to create a safe and respectful environment for patient partners may not come naturally to researchers, who should learn these skills or get training.

Seventh, give patient partners the information and training they need to participate, including awareness of ethical issues such as confidentiality, privacy, and legislation.

Eighth, recognize the contributions of patient research partners, which is usually voluntary work.

The authors reported having no relevant conflicts of interest.

New recommendations from the European League Against Rheumatism provide structure to the growing practice of including patient representatives in research projects.

The recommendations should be useful not only within the European League Against Rheumatism (EULAR) but also to other medical researchers, Maarten P. T. de Wit of Vrije Universiteit Medical Centre, Amsterdam, and his associates reported. EULAR convened a 16-member task force that crafted eight recommendations to promote inclusion of the patient perspective in EULAR-funded scientific research (Ann. Rheum. Dis. 2011[doi:10.1136/ard.2010.135129]).

Some previous reports suggest that the benefits of including patient representatives in research outweigh the drawbacks. Although including one or more patient representatives has become “usual practice” in EULAR scientific projects, the League's standardized procedures previously have not described how best to do this, the task force said.

They defined patient research partners as “persons with a relevant disease who operate as active research team members on an equal basis with professional researchers, adding the benefit of their experiential knowledge to any phase of the project.” Including patient research partners can help prevent mismatches between patient preferences and the focus of research, lead to more patient-oriented research agendas, empower patients, and build trust between patient organizations and medical institutions, data suggest.

The task force of three rheumatologists, one rheumatologist/epidemiologist, two allied health professionals, two research organization representatives, and eight patient research partners from six countries reviewed the literature and met twice to develop the recommendations, which were then evaluated by 28 patient representatives and 53 health professionals.

First, the task force urged that clinical researchers and groups work with patient research partners when developing guidelines or recommendations, and that other researchers consider patient participation. Patients' experiential knowledge is important even for laboratory-based research, and researchers who do not include patient partners should justify that decision, they said.

Second, patient participation should be considered for all phases of a research project and is essential in the early stages of research when critical decisions about the protocol and project are made. If this recommendation is not followed, investigators should explain why when publishing results.

Third, each project should include at least two patient research partners. There's no solid evidence to support this, but it adds to the team's diversity and supports the patient partners, and provides a substitute if one patient is absent due to rheumatic illness. This recommendation also drew more support from patients in the group of experts, winning agreement from 26 patients (93%) compared with 36 professionals (68%).

Fourth, give potential patient research partners a clear description of the minimum requirements for the position and clarify the roles of the patient partners and the principal investigator.

Fifth, take into account the patient's communication skills, motivation, and attitude when selecting patient research partners. Having a critical but constructive and proactive attitude is ideal. Academic training is not necessary and a medical background might even be undesirable, though some familiarity with medical terminology helps. “Thinking like an outsider is crucial to provide experiential knowledge,” the task force said.

Sixth, a good attitude, good communication, and good support from the principal investigator are crucial for the full participation of patient partners. These skills to create a safe and respectful environment for patient partners may not come naturally to researchers, who should learn these skills or get training.

Seventh, give patient partners the information and training they need to participate, including awareness of ethical issues such as confidentiality, privacy, and legislation.

Eighth, recognize the contributions of patient research partners, which is usually voluntary work.

The authors reported having no relevant conflicts of interest.

New recommendations from the European League Against Rheumatism provide structure to the growing practice of including patient representatives in research projects.

The recommendations should be useful not only within the European League Against Rheumatism (EULAR) but also to other medical researchers, Maarten P. T. de Wit of Vrije Universiteit Medical Centre, Amsterdam, and his associates reported. EULAR convened a 16-member task force that crafted eight recommendations to promote inclusion of the patient perspective in EULAR-funded scientific research (Ann. Rheum. Dis. 2011[doi:10.1136/ard.2010.135129]).

Some previous reports suggest that the benefits of including patient representatives in research outweigh the drawbacks. Although including one or more patient representatives has become “usual practice” in EULAR scientific projects, the League's standardized procedures previously have not described how best to do this, the task force said.

They defined patient research partners as “persons with a relevant disease who operate as active research team members on an equal basis with professional researchers, adding the benefit of their experiential knowledge to any phase of the project.” Including patient research partners can help prevent mismatches between patient preferences and the focus of research, lead to more patient-oriented research agendas, empower patients, and build trust between patient organizations and medical institutions, data suggest.

The task force of three rheumatologists, one rheumatologist/epidemiologist, two allied health professionals, two research organization representatives, and eight patient research partners from six countries reviewed the literature and met twice to develop the recommendations, which were then evaluated by 28 patient representatives and 53 health professionals.

First, the task force urged that clinical researchers and groups work with patient research partners when developing guidelines or recommendations, and that other researchers consider patient participation. Patients' experiential knowledge is important even for laboratory-based research, and researchers who do not include patient partners should justify that decision, they said.

Second, patient participation should be considered for all phases of a research project and is essential in the early stages of research when critical decisions about the protocol and project are made. If this recommendation is not followed, investigators should explain why when publishing results.

Third, each project should include at least two patient research partners. There's no solid evidence to support this, but it adds to the team's diversity and supports the patient partners, and provides a substitute if one patient is absent due to rheumatic illness. This recommendation also drew more support from patients in the group of experts, winning agreement from 26 patients (93%) compared with 36 professionals (68%).

Fourth, give potential patient research partners a clear description of the minimum requirements for the position and clarify the roles of the patient partners and the principal investigator.

Fifth, take into account the patient's communication skills, motivation, and attitude when selecting patient research partners. Having a critical but constructive and proactive attitude is ideal. Academic training is not necessary and a medical background might even be undesirable, though some familiarity with medical terminology helps. “Thinking like an outsider is crucial to provide experiential knowledge,” the task force said.

Sixth, a good attitude, good communication, and good support from the principal investigator are crucial for the full participation of patient partners. These skills to create a safe and respectful environment for patient partners may not come naturally to researchers, who should learn these skills or get training.

Seventh, give patient partners the information and training they need to participate, including awareness of ethical issues such as confidentiality, privacy, and legislation.

Eighth, recognize the contributions of patient research partners, which is usually voluntary work.

The authors reported having no relevant conflicts of interest.

BETHESDA, MD. — Evidence-based nonpharmacologic therapies may be at least as effective as medications in treating chronic pain, and the Internet could prove to be a valuable method for delivering these interventions.

Although pharmacologic agents alone are of only modest benefit and rarely lead to clinically meaningful functional improvement among patients with chronic pain, there is strong evidence for nonpharmacologic therapies such as cognitive-behavioral therapy (CBT) in improving functional status and mood, as well as pain itself, David A. Williams, Ph.D., said at the meeting, sponsored by the University of Michigan and the National Institutes of Health.

A meta-analysis of 25 papers found that active psychological treatments based on the principle of CBT produced significantly greater improvements in pain experience, cognitive coping, appraisal, and behavioral expressions of pain, compared with other active treatments, in patients with a variety of chronic pain problems, excluding headache (Pain 1999;80:1-13).

Another meta-analysis, this one including 22 studies of adults with noncancerous chronic low back pain, found that psychological interventions – particularly CBT and self-regulatory treatments – significantly reduced pain intensity, pain-related interference, and depression while significantly improving health-related quality of life. Multidisciplinary approaches that included psychological interventions also had positive effects (Health Psychology 2007;26:1-9).

And two more meta-analyses – one of 49 studies, the other of 23 – have demonstrated an equal or greater effect for nonpharmacologic therapies compared with pharmacologic treatment for fibromyalgia (Ann. Behav. Med. 1999;21: 180-91; Pain 2010;151:280-95).

“There is a 30-year history of nonpharmacologic interventions that have rival effect sizes to some pharmacologic approaches and even surpass some. The problem is, [nonpharmacologic interventions are] rarely used in clinical practice,” explained Dr. Williams, professor of anesthesiology, medicine (rheumatology), psychiatry, and psychology and associate director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor.

The use of nonpharmacologic treatment has been limited for a variety of reasons.

Medical schools don't spend much time teaching it, insurance companies often don't adequately cover it, patients often can't access it, it lacks the million dollar marketing campaigns that pharmaceutical companies devote to their drugs, and it carries a stigma, he noted.

Delivering such evidence-based interventions via the Internet potentially sidesteps several of the barriers that prevent their wider use, including those of access, cost, convenience, and privacy.

Numerous pilot or small-scale studies have supported the efficacy and utility of this approach, with outcomes that are often consistent with or even greater than those identified when using traditional face-to-face modalities, Dr. Williams said.

The following are studies of Web-based interventions with evidence to support their efficacy. Some of the sites are now online, while others were developed in the context of academic research and are currently not available to the public:

E-Mail Discussion Groups

These early e-health efforts demonstrated significant benefit in a randomized controlled trial of 580 individuals with chronic low back pain, from 49 states. The intervention included a moderated e-mail discussion group combined with a workbook and videotape about back pain. Controls received a subscription to a nonhealth magazine of their choice. At 1 year, the e-mail group had significant improvements in pain, disability, role function, distress, and health care utilization (Arch. Intern. Med. 2002;162:792-6). h

Swedish Study

In this controlled trial, 56 patients with chronic low back pain were randomized to 8 weeks of either Internet-based CBT with telephone support or to a waiting list. Treatment included CBT modules involving relaxation, exercise and stretching, cognitive restructuring, activity pacing, and relapse prevention. Weekly telephone contact with a therapist related to the goals of the program and homework.

At 3 months, those who had treatment showed statistically significant improvements, compared with those on a waiting list, in control over pain, ability to decrease pain, and catastrophizing (Pain 2004;111:368-77).

WEBMAP

This one delivered CBT to the young. In a randomized controlled trial, 48 children aged 11-17 years who had chronic headache, abdominal, or musculoskeletal pain and associated functional disability were assigned with their parents to either an Internet treatment group or to a waiting list.

The Internet treatment group completed 8 weeks of online modules including relaxation training, cognitive strategies, parent operant techniques, communication strategies, and sleep and activity interventions, in separate sites for patients and parents.

Controls had only current medical care (Pain 2009;146:205-13).

There was a significantly greater reduction in activity limitations and pain intensity at post treatment for the Internet treatment group, which were maintained at a 3-month follow-up. Clinically significant lessening of pain was also greater for the Internet treatment group than for the waiting-list control group.

Teens Taking Charge

Another CBT-based site for young people, “Teens Taking Charge: Managing Arthritis Online” focuses specifically on those with juvenile idiopathic arthritis and their parents.

In a 12-week nonblinded, randomized controlled trial done at four centers in Canada, 46 adolescents aged 12-18 with JIA plus one parent each were randomized to the Internet intervention or control arm (J. Rheumatol. 2010;37:1944-52).

The CBT-based self-management modules, written specifically for teens, provide education about arthritis and symptom management, and also address areas such as relaxation, medications, distraction, and managing thoughts. A journal page allows the teen to track progress. Two modules for parents focus on arthritis impact and “letting go.” Multimedia components include more than 300 pages of content, including Flash animation, video, forums for teens and parents, surveys, and weekly quizzes. The online “coach” has a BA degree in psychology.

At posttreatment, the intervention group had significantly better knowledge and lower average weekly pain intensity.

painAction

This interactive self-management Web site for people with chronic back pain was evaluated in a pretest-posttest controlled trial in which 209 patients were randomized to either the site (

www.painaction.com

The site was based on CBT and self-management principles, including collaborative decision making, goal setting, problem solving, relapse prevention, nutrition, stress management, and exercise. As with many of the other sites, this one included interactive tools, personalized assessments, and a library of articles.

At 6 months, clinically significant changes were seen in pain, depression, anxiety, and global ratings of improvement among those randomized to the site, which is supported by Endo Pharmaceuticals Inc. and King Pharmaceuticals Inc.

Living Well With Fibromyalgia

From Dr. Williams' group at the University of Michigan, this Internet-based exercise and behavioral self-management program for fibromyalgia was designed for use in the context of clinical care. A total of 118 patients were randomized to the program plus standard care, or standard care alone (Pain 2010;151:694-702).

Among the site's features are CBT modules including educational material about fibromyalgia and its treatment; symptom management with modalities including medications, exercise, sleep, and relaxation; and lifestyle changes including goal setting, problem solving, and graded activation.

Multimedia tools include video lectures by professionals, downloadable worksheets, self-monitoring forms, and audio recordings of exercises (

www.fibroguide.com

At 6 months, overall improvement was seen in 57% with the Web program vs. 21% with standard care alone.

The proportion experiencing 30% pain improvement or greater (pain responders) was 29% vs. 8% with standard care alone, and functional improvement, defined as an improvement of 0.5 standard deviations, was seen in 31% vs. 6%. All differences were statistically significant, and the number needed to treat for both outcomes was 5, better than the typical 7-19 seen in pharmaceutical trials, Dr. Williams noted.

In a recent meta-analysis of 11 studies of Web-based interventions for chronic pain that used pain scale scores as the main outcome, the standardized mean difference between intervention and waiting-list group means was 0.285, favoring the Web interventions but with a small effect size (J. Pain 2010;11:917-29).

“Broader adoption of this method of delivering care for pain needs to be moved to the next level in terms of both infrastructure and practitioner consensus,” Dr. Williams said in an interview.

“Hopes of expanding Internet-based behavioral treatment for pain would need to contain content reflecting a broader consensus of experts from the various disciplines associated with pain management,” he said.

“Currently there is great interest in developing such resources both in the public and private sectors.

“This appears to be a valuable approach to supplying individuals with an aspect of effective pain management that is often missing.”

Dr. Williams is a consultant for Eli Lilly & Co., Forest Pharmaceuticals, and Bristol-Myers Squibb.

BETHESDA, MD. — Evidence-based nonpharmacologic therapies may be at least as effective as medications in treating chronic pain, and the Internet could prove to be a valuable method for delivering these interventions.

Although pharmacologic agents alone are of only modest benefit and rarely lead to clinically meaningful functional improvement among patients with chronic pain, there is strong evidence for nonpharmacologic therapies such as cognitive-behavioral therapy (CBT) in improving functional status and mood, as well as pain itself, David A. Williams, Ph.D., said at the meeting, sponsored by the University of Michigan and the National Institutes of Health.

A meta-analysis of 25 papers found that active psychological treatments based on the principle of CBT produced significantly greater improvements in pain experience, cognitive coping, appraisal, and behavioral expressions of pain, compared with other active treatments, in patients with a variety of chronic pain problems, excluding headache (Pain 1999;80:1-13).

Another meta-analysis, this one including 22 studies of adults with noncancerous chronic low back pain, found that psychological interventions – particularly CBT and self-regulatory treatments – significantly reduced pain intensity, pain-related interference, and depression while significantly improving health-related quality of life. Multidisciplinary approaches that included psychological interventions also had positive effects (Health Psychology 2007;26:1-9).

And two more meta-analyses – one of 49 studies, the other of 23 – have demonstrated an equal or greater effect for nonpharmacologic therapies compared with pharmacologic treatment for fibromyalgia (Ann. Behav. Med. 1999;21: 180-91; Pain 2010;151:280-95).

“There is a 30-year history of nonpharmacologic interventions that have rival effect sizes to some pharmacologic approaches and even surpass some. The problem is, [nonpharmacologic interventions are] rarely used in clinical practice,” explained Dr. Williams, professor of anesthesiology, medicine (rheumatology), psychiatry, and psychology and associate director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor.

The use of nonpharmacologic treatment has been limited for a variety of reasons.

Medical schools don't spend much time teaching it, insurance companies often don't adequately cover it, patients often can't access it, it lacks the million dollar marketing campaigns that pharmaceutical companies devote to their drugs, and it carries a stigma, he noted.

Delivering such evidence-based interventions via the Internet potentially sidesteps several of the barriers that prevent their wider use, including those of access, cost, convenience, and privacy.

Numerous pilot or small-scale studies have supported the efficacy and utility of this approach, with outcomes that are often consistent with or even greater than those identified when using traditional face-to-face modalities, Dr. Williams said.

The following are studies of Web-based interventions with evidence to support their efficacy. Some of the sites are now online, while others were developed in the context of academic research and are currently not available to the public:

E-Mail Discussion Groups

These early e-health efforts demonstrated significant benefit in a randomized controlled trial of 580 individuals with chronic low back pain, from 49 states. The intervention included a moderated e-mail discussion group combined with a workbook and videotape about back pain. Controls received a subscription to a nonhealth magazine of their choice. At 1 year, the e-mail group had significant improvements in pain, disability, role function, distress, and health care utilization (Arch. Intern. Med. 2002;162:792-6). h

Swedish Study

In this controlled trial, 56 patients with chronic low back pain were randomized to 8 weeks of either Internet-based CBT with telephone support or to a waiting list. Treatment included CBT modules involving relaxation, exercise and stretching, cognitive restructuring, activity pacing, and relapse prevention. Weekly telephone contact with a therapist related to the goals of the program and homework.

At 3 months, those who had treatment showed statistically significant improvements, compared with those on a waiting list, in control over pain, ability to decrease pain, and catastrophizing (Pain 2004;111:368-77).

WEBMAP

This one delivered CBT to the young. In a randomized controlled trial, 48 children aged 11-17 years who had chronic headache, abdominal, or musculoskeletal pain and associated functional disability were assigned with their parents to either an Internet treatment group or to a waiting list.

The Internet treatment group completed 8 weeks of online modules including relaxation training, cognitive strategies, parent operant techniques, communication strategies, and sleep and activity interventions, in separate sites for patients and parents.

Controls had only current medical care (Pain 2009;146:205-13).

There was a significantly greater reduction in activity limitations and pain intensity at post treatment for the Internet treatment group, which were maintained at a 3-month follow-up. Clinically significant lessening of pain was also greater for the Internet treatment group than for the waiting-list control group.

Teens Taking Charge

Another CBT-based site for young people, “Teens Taking Charge: Managing Arthritis Online” focuses specifically on those with juvenile idiopathic arthritis and their parents.

In a 12-week nonblinded, randomized controlled trial done at four centers in Canada, 46 adolescents aged 12-18 with JIA plus one parent each were randomized to the Internet intervention or control arm (J. Rheumatol. 2010;37:1944-52).

The CBT-based self-management modules, written specifically for teens, provide education about arthritis and symptom management, and also address areas such as relaxation, medications, distraction, and managing thoughts. A journal page allows the teen to track progress. Two modules for parents focus on arthritis impact and “letting go.” Multimedia components include more than 300 pages of content, including Flash animation, video, forums for teens and parents, surveys, and weekly quizzes. The online “coach” has a BA degree in psychology.

At posttreatment, the intervention group had significantly better knowledge and lower average weekly pain intensity.

painAction

This interactive self-management Web site for people with chronic back pain was evaluated in a pretest-posttest controlled trial in which 209 patients were randomized to either the site (

www.painaction.com

The site was based on CBT and self-management principles, including collaborative decision making, goal setting, problem solving, relapse prevention, nutrition, stress management, and exercise. As with many of the other sites, this one included interactive tools, personalized assessments, and a library of articles.

At 6 months, clinically significant changes were seen in pain, depression, anxiety, and global ratings of improvement among those randomized to the site, which is supported by Endo Pharmaceuticals Inc. and King Pharmaceuticals Inc.

Living Well With Fibromyalgia

From Dr. Williams' group at the University of Michigan, this Internet-based exercise and behavioral self-management program for fibromyalgia was designed for use in the context of clinical care. A total of 118 patients were randomized to the program plus standard care, or standard care alone (Pain 2010;151:694-702).

Among the site's features are CBT modules including educational material about fibromyalgia and its treatment; symptom management with modalities including medications, exercise, sleep, and relaxation; and lifestyle changes including goal setting, problem solving, and graded activation.

Multimedia tools include video lectures by professionals, downloadable worksheets, self-monitoring forms, and audio recordings of exercises (

www.fibroguide.com

At 6 months, overall improvement was seen in 57% with the Web program vs. 21% with standard care alone.

The proportion experiencing 30% pain improvement or greater (pain responders) was 29% vs. 8% with standard care alone, and functional improvement, defined as an improvement of 0.5 standard deviations, was seen in 31% vs. 6%. All differences were statistically significant, and the number needed to treat for both outcomes was 5, better than the typical 7-19 seen in pharmaceutical trials, Dr. Williams noted.

In a recent meta-analysis of 11 studies of Web-based interventions for chronic pain that used pain scale scores as the main outcome, the standardized mean difference between intervention and waiting-list group means was 0.285, favoring the Web interventions but with a small effect size (J. Pain 2010;11:917-29).

“Broader adoption of this method of delivering care for pain needs to be moved to the next level in terms of both infrastructure and practitioner consensus,” Dr. Williams said in an interview.

“Hopes of expanding Internet-based behavioral treatment for pain would need to contain content reflecting a broader consensus of experts from the various disciplines associated with pain management,” he said.

“Currently there is great interest in developing such resources both in the public and private sectors.

“This appears to be a valuable approach to supplying individuals with an aspect of effective pain management that is often missing.”

Dr. Williams is a consultant for Eli Lilly & Co., Forest Pharmaceuticals, and Bristol-Myers Squibb.

BETHESDA, MD. — Evidence-based nonpharmacologic therapies may be at least as effective as medications in treating chronic pain, and the Internet could prove to be a valuable method for delivering these interventions.

Although pharmacologic agents alone are of only modest benefit and rarely lead to clinically meaningful functional improvement among patients with chronic pain, there is strong evidence for nonpharmacologic therapies such as cognitive-behavioral therapy (CBT) in improving functional status and mood, as well as pain itself, David A. Williams, Ph.D., said at the meeting, sponsored by the University of Michigan and the National Institutes of Health.

A meta-analysis of 25 papers found that active psychological treatments based on the principle of CBT produced significantly greater improvements in pain experience, cognitive coping, appraisal, and behavioral expressions of pain, compared with other active treatments, in patients with a variety of chronic pain problems, excluding headache (Pain 1999;80:1-13).

Another meta-analysis, this one including 22 studies of adults with noncancerous chronic low back pain, found that psychological interventions – particularly CBT and self-regulatory treatments – significantly reduced pain intensity, pain-related interference, and depression while significantly improving health-related quality of life. Multidisciplinary approaches that included psychological interventions also had positive effects (Health Psychology 2007;26:1-9).

And two more meta-analyses – one of 49 studies, the other of 23 – have demonstrated an equal or greater effect for nonpharmacologic therapies compared with pharmacologic treatment for fibromyalgia (Ann. Behav. Med. 1999;21: 180-91; Pain 2010;151:280-95).

“There is a 30-year history of nonpharmacologic interventions that have rival effect sizes to some pharmacologic approaches and even surpass some. The problem is, [nonpharmacologic interventions are] rarely used in clinical practice,” explained Dr. Williams, professor of anesthesiology, medicine (rheumatology), psychiatry, and psychology and associate director of the chronic pain and fatigue research center at the University of Michigan, Ann Arbor.

The use of nonpharmacologic treatment has been limited for a variety of reasons.

Medical schools don't spend much time teaching it, insurance companies often don't adequately cover it, patients often can't access it, it lacks the million dollar marketing campaigns that pharmaceutical companies devote to their drugs, and it carries a stigma, he noted.

Delivering such evidence-based interventions via the Internet potentially sidesteps several of the barriers that prevent their wider use, including those of access, cost, convenience, and privacy.

Numerous pilot or small-scale studies have supported the efficacy and utility of this approach, with outcomes that are often consistent with or even greater than those identified when using traditional face-to-face modalities, Dr. Williams said.

The following are studies of Web-based interventions with evidence to support their efficacy. Some of the sites are now online, while others were developed in the context of academic research and are currently not available to the public:

E-Mail Discussion Groups

These early e-health efforts demonstrated significant benefit in a randomized controlled trial of 580 individuals with chronic low back pain, from 49 states. The intervention included a moderated e-mail discussion group combined with a workbook and videotape about back pain. Controls received a subscription to a nonhealth magazine of their choice. At 1 year, the e-mail group had significant improvements in pain, disability, role function, distress, and health care utilization (Arch. Intern. Med. 2002;162:792-6). h

Swedish Study

In this controlled trial, 56 patients with chronic low back pain were randomized to 8 weeks of either Internet-based CBT with telephone support or to a waiting list. Treatment included CBT modules involving relaxation, exercise and stretching, cognitive restructuring, activity pacing, and relapse prevention. Weekly telephone contact with a therapist related to the goals of the program and homework.

At 3 months, those who had treatment showed statistically significant improvements, compared with those on a waiting list, in control over pain, ability to decrease pain, and catastrophizing (Pain 2004;111:368-77).

WEBMAP

This one delivered CBT to the young. In a randomized controlled trial, 48 children aged 11-17 years who had chronic headache, abdominal, or musculoskeletal pain and associated functional disability were assigned with their parents to either an Internet treatment group or to a waiting list.

The Internet treatment group completed 8 weeks of online modules including relaxation training, cognitive strategies, parent operant techniques, communication strategies, and sleep and activity interventions, in separate sites for patients and parents.

Controls had only current medical care (Pain 2009;146:205-13).

There was a significantly greater reduction in activity limitations and pain intensity at post treatment for the Internet treatment group, which were maintained at a 3-month follow-up. Clinically significant lessening of pain was also greater for the Internet treatment group than for the waiting-list control group.

Teens Taking Charge

Another CBT-based site for young people, “Teens Taking Charge: Managing Arthritis Online” focuses specifically on those with juvenile idiopathic arthritis and their parents.

In a 12-week nonblinded, randomized controlled trial done at four centers in Canada, 46 adolescents aged 12-18 with JIA plus one parent each were randomized to the Internet intervention or control arm (J. Rheumatol. 2010;37:1944-52).

The CBT-based self-management modules, written specifically for teens, provide education about arthritis and symptom management, and also address areas such as relaxation, medications, distraction, and managing thoughts. A journal page allows the teen to track progress. Two modules for parents focus on arthritis impact and “letting go.” Multimedia components include more than 300 pages of content, including Flash animation, video, forums for teens and parents, surveys, and weekly quizzes. The online “coach” has a BA degree in psychology.

At posttreatment, the intervention group had significantly better knowledge and lower average weekly pain intensity.

painAction

This interactive self-management Web site for people with chronic back pain was evaluated in a pretest-posttest controlled trial in which 209 patients were randomized to either the site (

www.painaction.com

The site was based on CBT and self-management principles, including collaborative decision making, goal setting, problem solving, relapse prevention, nutrition, stress management, and exercise. As with many of the other sites, this one included interactive tools, personalized assessments, and a library of articles.

At 6 months, clinically significant changes were seen in pain, depression, anxiety, and global ratings of improvement among those randomized to the site, which is supported by Endo Pharmaceuticals Inc. and King Pharmaceuticals Inc.

Living Well With Fibromyalgia

From Dr. Williams' group at the University of Michigan, this Internet-based exercise and behavioral self-management program for fibromyalgia was designed for use in the context of clinical care. A total of 118 patients were randomized to the program plus standard care, or standard care alone (Pain 2010;151:694-702).

Among the site's features are CBT modules including educational material about fibromyalgia and its treatment; symptom management with modalities including medications, exercise, sleep, and relaxation; and lifestyle changes including goal setting, problem solving, and graded activation.

Multimedia tools include video lectures by professionals, downloadable worksheets, self-monitoring forms, and audio recordings of exercises (

www.fibroguide.com

At 6 months, overall improvement was seen in 57% with the Web program vs. 21% with standard care alone.

The proportion experiencing 30% pain improvement or greater (pain responders) was 29% vs. 8% with standard care alone, and functional improvement, defined as an improvement of 0.5 standard deviations, was seen in 31% vs. 6%. All differences were statistically significant, and the number needed to treat for both outcomes was 5, better than the typical 7-19 seen in pharmaceutical trials, Dr. Williams noted.

In a recent meta-analysis of 11 studies of Web-based interventions for chronic pain that used pain scale scores as the main outcome, the standardized mean difference between intervention and waiting-list group means was 0.285, favoring the Web interventions but with a small effect size (J. Pain 2010;11:917-29).

“Broader adoption of this method of delivering care for pain needs to be moved to the next level in terms of both infrastructure and practitioner consensus,” Dr. Williams said in an interview.

“Hopes of expanding Internet-based behavioral treatment for pain would need to contain content reflecting a broader consensus of experts from the various disciplines associated with pain management,” he said.

“Currently there is great interest in developing such resources both in the public and private sectors.

“This appears to be a valuable approach to supplying individuals with an aspect of effective pain management that is often missing.”

Dr. Williams is a consultant for Eli Lilly & Co., Forest Pharmaceuticals, and Bristol-Myers Squibb.

VANCOUVER, B.C. — New-onset pulmonary abnormalities in patients with rheumatoid arthritis should keep rheumatologists and pulmonologists on the edge of their seats, clinically speaking. The lung is a frequent site of extra-articular arthritis, and its most common manifestation – interstitial lung disease – carries significant morbidity and mortality risks, according to Dr. Kevin R. Flaherty.

Pulmonary Manifestations of RA

The lifetime risk of interstitial lung disease is nearly 8% in patients with RA, compared with 1% in the general population (Arthritis Rheum. 2010;62:1583-91).

And this disease confers a poor prognosis, with a near tripling of the risk of death and with a median survival after diagnosis of 2.5 years, noted Dr. Flaherty, who is a pulmonologist and associate professor at the University of Michigan Health System in Ann Arbor.

High-resolution computed tomography (HRCT) and pulmonary functioning testing appear to be useful for identifying interstitial lung disease early in its course, according to Dr. Flaherty.

For example, among patients within 2 years of a RA diagnosis, 44% have been found to have HRCT, pulmonary function test, and other abnormalities consistent with interstitial lung disease in the absence of symptoms (Am. J. Respir. Crit. Care Med. 1997;156:528-35).

“The [HRCT] features were mild – reticular thickening, ground glass, and not much honeycombing – suggesting maybe that we might be able to impact the disease, because I think once you get to honeycomb lung and end-stage fibrosis, our ability to impact this disease is likely to be lower,” he said.

As for which patients to screen for interstitial lung disease, the predictors of abnormal pulmonary function testing in the RA population are respiratory symptoms, smoking, anti–cyclic citrullinated peptide positivity, and use of prednisone (Arthritis Res. Ther. 2010;12:R104).

When it comes to monitoring interstitial lung disease, HRCT appears to be more sensitive than pulmonary function testing for detecting disease progression (Arch. Intern. Med. 2008;168:159-66).

And carbon monoxide diffusing capacity at diagnosis is the best predictor of progression (Ann. Rheum. Dis. 2002;61:517-21).

“We are starting … to see data emerging that really mirrors what we see in idiopathic lung disease, that the histopathology and the CT appearance can help us in terms of stratifying patients for risk of subsequent mortality,” Dr. Flaherty said.

A study of patients with RA-associated interstitial lung disease found 50% mortality in those with a usual interstitial pneumonia (UIP) histology, compared with none in those with a nonspecific interstitial pneumonia (NSIP) histology after a similar median follow-up of about 4 years (Chest 2005;127:2019-27).

A honeycomb pattern on HRCT was found only in the UIP group, suggesting that this radiographic pattern is a good surrogate for this histology, Dr. Flaherty noted. And indeed, patients having a definite UIP radiographic appearance have poorer survival (Eur. Respir. J. 2010;35:1322-8).

Rigorous studies are lacking when it comes to treating interstitial lung disease in the RA population, according to Dr. Flaherty.

Pulmonary Adverse Effects of RA Therapy

Pneumonitis is often a concern in patients using methotrexate to treat RA. But with low-dose therapy, only 3% of patients develop this complication after a mean treatment duration of 23 months (Chest 1996;109:933-8), Dr. Flaherty pointed out.

Anti–tumor necrosis factor agents such as infliximab have been associated with pulmonary adverse effects and complications, including infection, atypical presentation of tuberculosis, and pulmonary fibrosis.

Some research reports have also raised concern that anti-TNF agents may hasten progression of interstitial lung disease in patients with RA and thus increase mortality.

“The data on that are still out,” Dr. Flaherty said. Evidence thus far suggests that mortality in patients treated with these agents is similar to that in their counterparts treated with traditional disease-modifying antirheumatic drugs (Ann. Rheum. Dis. 2010;69:1086-91).

Rituximab has been linked to severe infections in patients with RA, the largest share of which (40%) are pulmonary (Arthritis Rheum. 2010;62:2625-32). Only a single infection was opportunistic, and most were bacterial.

Pulmonary Cancers

Patients with RA have increased risk of lung cancer (standardized incidence ratio, 1.63) as well as for another malignancy that can involve the lung, lymphoma (Arthritis Res. Ther. 2008;10:R45), as a result of their underlying disease, long-term immunosuppression, or both.

Treatment with biologic agents has not been associated with a significantly elevated risk of lung cancer among patients with RA, according to Dr. Flaherty.

But treatment with methotrexate has, with the incidence of lung cancer among methotrexate users about triple that of the general population (Arthritis Rheum. 2008;59:794-9).

Users of this drug also have sharply increased rates of non-Hodgkin's lymphoma and melanoma.

Dr. Flaherty did not report any disclosures.

VANCOUVER, B.C. — New-onset pulmonary abnormalities in patients with rheumatoid arthritis should keep rheumatologists and pulmonologists on the edge of their seats, clinically speaking. The lung is a frequent site of extra-articular arthritis, and its most common manifestation – interstitial lung disease – carries significant morbidity and mortality risks, according to Dr. Kevin R. Flaherty.

Pulmonary Manifestations of RA

The lifetime risk of interstitial lung disease is nearly 8% in patients with RA, compared with 1% in the general population (Arthritis Rheum. 2010;62:1583-91).

And this disease confers a poor prognosis, with a near tripling of the risk of death and with a median survival after diagnosis of 2.5 years, noted Dr. Flaherty, who is a pulmonologist and associate professor at the University of Michigan Health System in Ann Arbor.

High-resolution computed tomography (HRCT) and pulmonary functioning testing appear to be useful for identifying interstitial lung disease early in its course, according to Dr. Flaherty.

For example, among patients within 2 years of a RA diagnosis, 44% have been found to have HRCT, pulmonary function test, and other abnormalities consistent with interstitial lung disease in the absence of symptoms (Am. J. Respir. Crit. Care Med. 1997;156:528-35).

“The [HRCT] features were mild – reticular thickening, ground glass, and not much honeycombing – suggesting maybe that we might be able to impact the disease, because I think once you get to honeycomb lung and end-stage fibrosis, our ability to impact this disease is likely to be lower,” he said.

As for which patients to screen for interstitial lung disease, the predictors of abnormal pulmonary function testing in the RA population are respiratory symptoms, smoking, anti–cyclic citrullinated peptide positivity, and use of prednisone (Arthritis Res. Ther. 2010;12:R104).

When it comes to monitoring interstitial lung disease, HRCT appears to be more sensitive than pulmonary function testing for detecting disease progression (Arch. Intern. Med. 2008;168:159-66).

And carbon monoxide diffusing capacity at diagnosis is the best predictor of progression (Ann. Rheum. Dis. 2002;61:517-21).

“We are starting … to see data emerging that really mirrors what we see in idiopathic lung disease, that the histopathology and the CT appearance can help us in terms of stratifying patients for risk of subsequent mortality,” Dr. Flaherty said.

A study of patients with RA-associated interstitial lung disease found 50% mortality in those with a usual interstitial pneumonia (UIP) histology, compared with none in those with a nonspecific interstitial pneumonia (NSIP) histology after a similar median follow-up of about 4 years (Chest 2005;127:2019-27).

A honeycomb pattern on HRCT was found only in the UIP group, suggesting that this radiographic pattern is a good surrogate for this histology, Dr. Flaherty noted. And indeed, patients having a definite UIP radiographic appearance have poorer survival (Eur. Respir. J. 2010;35:1322-8).

Rigorous studies are lacking when it comes to treating interstitial lung disease in the RA population, according to Dr. Flaherty.

Pulmonary Adverse Effects of RA Therapy

Pneumonitis is often a concern in patients using methotrexate to treat RA. But with low-dose therapy, only 3% of patients develop this complication after a mean treatment duration of 23 months (Chest 1996;109:933-8), Dr. Flaherty pointed out.

Anti–tumor necrosis factor agents such as infliximab have been associated with pulmonary adverse effects and complications, including infection, atypical presentation of tuberculosis, and pulmonary fibrosis.

Some research reports have also raised concern that anti-TNF agents may hasten progression of interstitial lung disease in patients with RA and thus increase mortality.

“The data on that are still out,” Dr. Flaherty said. Evidence thus far suggests that mortality in patients treated with these agents is similar to that in their counterparts treated with traditional disease-modifying antirheumatic drugs (Ann. Rheum. Dis. 2010;69:1086-91).

Rituximab has been linked to severe infections in patients with RA, the largest share of which (40%) are pulmonary (Arthritis Rheum. 2010;62:2625-32). Only a single infection was opportunistic, and most were bacterial.

Pulmonary Cancers

Patients with RA have increased risk of lung cancer (standardized incidence ratio, 1.63) as well as for another malignancy that can involve the lung, lymphoma (Arthritis Res. Ther. 2008;10:R45), as a result of their underlying disease, long-term immunosuppression, or both.

Treatment with biologic agents has not been associated with a significantly elevated risk of lung cancer among patients with RA, according to Dr. Flaherty.

But treatment with methotrexate has, with the incidence of lung cancer among methotrexate users about triple that of the general population (Arthritis Rheum. 2008;59:794-9).

Users of this drug also have sharply increased rates of non-Hodgkin's lymphoma and melanoma.

Dr. Flaherty did not report any disclosures.

VANCOUVER, B.C. — New-onset pulmonary abnormalities in patients with rheumatoid arthritis should keep rheumatologists and pulmonologists on the edge of their seats, clinically speaking. The lung is a frequent site of extra-articular arthritis, and its most common manifestation – interstitial lung disease – carries significant morbidity and mortality risks, according to Dr. Kevin R. Flaherty.

Pulmonary Manifestations of RA

The lifetime risk of interstitial lung disease is nearly 8% in patients with RA, compared with 1% in the general population (Arthritis Rheum. 2010;62:1583-91).

And this disease confers a poor prognosis, with a near tripling of the risk of death and with a median survival after diagnosis of 2.5 years, noted Dr. Flaherty, who is a pulmonologist and associate professor at the University of Michigan Health System in Ann Arbor.

High-resolution computed tomography (HRCT) and pulmonary functioning testing appear to be useful for identifying interstitial lung disease early in its course, according to Dr. Flaherty.

For example, among patients within 2 years of a RA diagnosis, 44% have been found to have HRCT, pulmonary function test, and other abnormalities consistent with interstitial lung disease in the absence of symptoms (Am. J. Respir. Crit. Care Med. 1997;156:528-35).

“The [HRCT] features were mild – reticular thickening, ground glass, and not much honeycombing – suggesting maybe that we might be able to impact the disease, because I think once you get to honeycomb lung and end-stage fibrosis, our ability to impact this disease is likely to be lower,” he said.

As for which patients to screen for interstitial lung disease, the predictors of abnormal pulmonary function testing in the RA population are respiratory symptoms, smoking, anti–cyclic citrullinated peptide positivity, and use of prednisone (Arthritis Res. Ther. 2010;12:R104).

When it comes to monitoring interstitial lung disease, HRCT appears to be more sensitive than pulmonary function testing for detecting disease progression (Arch. Intern. Med. 2008;168:159-66).

And carbon monoxide diffusing capacity at diagnosis is the best predictor of progression (Ann. Rheum. Dis. 2002;61:517-21).

“We are starting … to see data emerging that really mirrors what we see in idiopathic lung disease, that the histopathology and the CT appearance can help us in terms of stratifying patients for risk of subsequent mortality,” Dr. Flaherty said.

A study of patients with RA-associated interstitial lung disease found 50% mortality in those with a usual interstitial pneumonia (UIP) histology, compared with none in those with a nonspecific interstitial pneumonia (NSIP) histology after a similar median follow-up of about 4 years (Chest 2005;127:2019-27).

A honeycomb pattern on HRCT was found only in the UIP group, suggesting that this radiographic pattern is a good surrogate for this histology, Dr. Flaherty noted. And indeed, patients having a definite UIP radiographic appearance have poorer survival (Eur. Respir. J. 2010;35:1322-8).

Rigorous studies are lacking when it comes to treating interstitial lung disease in the RA population, according to Dr. Flaherty.

Pulmonary Adverse Effects of RA Therapy

Pneumonitis is often a concern in patients using methotrexate to treat RA. But with low-dose therapy, only 3% of patients develop this complication after a mean treatment duration of 23 months (Chest 1996;109:933-8), Dr. Flaherty pointed out.

Anti–tumor necrosis factor agents such as infliximab have been associated with pulmonary adverse effects and complications, including infection, atypical presentation of tuberculosis, and pulmonary fibrosis.

Some research reports have also raised concern that anti-TNF agents may hasten progression of interstitial lung disease in patients with RA and thus increase mortality.

“The data on that are still out,” Dr. Flaherty said. Evidence thus far suggests that mortality in patients treated with these agents is similar to that in their counterparts treated with traditional disease-modifying antirheumatic drugs (Ann. Rheum. Dis. 2010;69:1086-91).

Rituximab has been linked to severe infections in patients with RA, the largest share of which (40%) are pulmonary (Arthritis Rheum. 2010;62:2625-32). Only a single infection was opportunistic, and most were bacterial.

Pulmonary Cancers

Patients with RA have increased risk of lung cancer (standardized incidence ratio, 1.63) as well as for another malignancy that can involve the lung, lymphoma (Arthritis Res. Ther. 2008;10:R45), as a result of their underlying disease, long-term immunosuppression, or both.

Treatment with biologic agents has not been associated with a significantly elevated risk of lung cancer among patients with RA, according to Dr. Flaherty.

But treatment with methotrexate has, with the incidence of lung cancer among methotrexate users about triple that of the general population (Arthritis Rheum. 2008;59:794-9).

Users of this drug also have sharply increased rates of non-Hodgkin's lymphoma and melanoma.

Dr. Flaherty did not report any disclosures.

Two imaging modalities independently predicted progressive joint erosion in patients with early rheumatoid arthritis as a group, but the tests performed only slightly better than did clinical and demographic variables for individual prognoses, judging from findings of a 1-year study.

Among 79 patients who completed quarterly follow-ups with a battery of imaging and nonimaging measures, 53 (67%) showed erosive progression. On a group level, results of ultrasound gray-scale (USGS) findings of inflammation and magnetic resonance images showing bone marrow edema each were significant predictors that erosive disease progression would be detected by MRI.

Patients with USGS inflammation in the dominant wrist were twice as likely to develop erosive progression and patients with MRI bone marrow edema in the dominant wrist were 28% more likely to develop erosive progression compared with patients without these imaging findings, Dr. Pernille Bøyesen and associates reported (Ann. Rheum. Dis. 2011;70:176-9 [doi: 10.1136/ard.2009. 126953]).

On an individual level, however, the imaging modalities were not dramatically better than clinical and demographic variables to predict erosive progression of early RA. USGS inflammation, synovitis on MRI, and bone marrow edema that was visible on MRI performed slightly better than using antibody to cyclic citrullinated protein, rheumatoid factor, and disease activity score based on a 28-joint count, reported Dr. Bøyesen of Diakonhjemmet Hospital, Oslo.

USGS inflammation was the best of 12 imaging modalities and measures of disease severity in identifying patients at risk of developing erosions on MRI, with a sensitivity of 78%, a specificity of 55%, a positive likelihood ration of 1.75, and accuracy of 70%.

Future studies are needed using composite indices of disease progression, including modern imaging modalities, to determine their value as predictors of an individual patient's likelihood of disease progression, the investigators concluded.

The study appears to be the first to confirm previous data suggesting that measuring inflammation by ultrasound can help predict subsequent joint damage, they noted. The findings also confirmed previous data identifying bone marrow edema on MRI as an independent predictor of joint damage.

Other imaging modalities in the study included digital x-ray radiogrammetry (DXR) of cortical bone mineral density in the hand. Results showed only trends toward higher levels of synovitis on MRI and bone density loss on DXR in patients with erosive progression of disease at 1 year. The findings did not support previous studies that reported cortical hand bone mineral density to be independently predictive of erosive progression, perhaps due to the small size of the study, Dr. Bøyesen added.

Given the comprehensive comparison of imaging modalities in the study, however, 84 patients can be considered a large number, the investigators noted.

The multivariate analyses controlled for the effects of age, sex, and other independent variables.

The investigators declared having no conflicts of interest. The study was funded by the Eastern Norway Regional Health Authority, the Research Council of Norway, the Norwegian Rheumatism Association, the Norwegian Women Public Health Association, the Grethe Harbitz Legacy, and the Marie and Else Mustad Legacy.

Baseline USGS (A) and 1-year MRI (B-D) of the radio-carpal joint are shown in a patient without erosive progression and in a patient with erosions (arrows) (E-H).

Source Courtesy Dr. Pernille Bøyesen

Two imaging modalities independently predicted progressive joint erosion in patients with early rheumatoid arthritis as a group, but the tests performed only slightly better than did clinical and demographic variables for individual prognoses, judging from findings of a 1-year study.

Among 79 patients who completed quarterly follow-ups with a battery of imaging and nonimaging measures, 53 (67%) showed erosive progression. On a group level, results of ultrasound gray-scale (USGS) findings of inflammation and magnetic resonance images showing bone marrow edema each were significant predictors that erosive disease progression would be detected by MRI.

Patients with USGS inflammation in the dominant wrist were twice as likely to develop erosive progression and patients with MRI bone marrow edema in the dominant wrist were 28% more likely to develop erosive progression compared with patients without these imaging findings, Dr. Pernille Bøyesen and associates reported (Ann. Rheum. Dis. 2011;70:176-9 [doi: 10.1136/ard.2009. 126953]).

On an individual level, however, the imaging modalities were not dramatically better than clinical and demographic variables to predict erosive progression of early RA. USGS inflammation, synovitis on MRI, and bone marrow edema that was visible on MRI performed slightly better than using antibody to cyclic citrullinated protein, rheumatoid factor, and disease activity score based on a 28-joint count, reported Dr. Bøyesen of Diakonhjemmet Hospital, Oslo.

USGS inflammation was the best of 12 imaging modalities and measures of disease severity in identifying patients at risk of developing erosions on MRI, with a sensitivity of 78%, a specificity of 55%, a positive likelihood ration of 1.75, and accuracy of 70%.

Future studies are needed using composite indices of disease progression, including modern imaging modalities, to determine their value as predictors of an individual patient's likelihood of disease progression, the investigators concluded.

The study appears to be the first to confirm previous data suggesting that measuring inflammation by ultrasound can help predict subsequent joint damage, they noted. The findings also confirmed previous data identifying bone marrow edema on MRI as an independent predictor of joint damage.

Other imaging modalities in the study included digital x-ray radiogrammetry (DXR) of cortical bone mineral density in the hand. Results showed only trends toward higher levels of synovitis on MRI and bone density loss on DXR in patients with erosive progression of disease at 1 year. The findings did not support previous studies that reported cortical hand bone mineral density to be independently predictive of erosive progression, perhaps due to the small size of the study, Dr. Bøyesen added.

Given the comprehensive comparison of imaging modalities in the study, however, 84 patients can be considered a large number, the investigators noted.

The multivariate analyses controlled for the effects of age, sex, and other independent variables.

The investigators declared having no conflicts of interest. The study was funded by the Eastern Norway Regional Health Authority, the Research Council of Norway, the Norwegian Rheumatism Association, the Norwegian Women Public Health Association, the Grethe Harbitz Legacy, and the Marie and Else Mustad Legacy.

Baseline USGS (A) and 1-year MRI (B-D) of the radio-carpal joint are shown in a patient without erosive progression and in a patient with erosions (arrows) (E-H).

Source Courtesy Dr. Pernille Bøyesen

Two imaging modalities independently predicted progressive joint erosion in patients with early rheumatoid arthritis as a group, but the tests performed only slightly better than did clinical and demographic variables for individual prognoses, judging from findings of a 1-year study.

Among 79 patients who completed quarterly follow-ups with a battery of imaging and nonimaging measures, 53 (67%) showed erosive progression. On a group level, results of ultrasound gray-scale (USGS) findings of inflammation and magnetic resonance images showing bone marrow edema each were significant predictors that erosive disease progression would be detected by MRI.

Patients with USGS inflammation in the dominant wrist were twice as likely to develop erosive progression and patients with MRI bone marrow edema in the dominant wrist were 28% more likely to develop erosive progression compared with patients without these imaging findings, Dr. Pernille Bøyesen and associates reported (Ann. Rheum. Dis. 2011;70:176-9 [doi: 10.1136/ard.2009. 126953]).

On an individual level, however, the imaging modalities were not dramatically better than clinical and demographic variables to predict erosive progression of early RA. USGS inflammation, synovitis on MRI, and bone marrow edema that was visible on MRI performed slightly better than using antibody to cyclic citrullinated protein, rheumatoid factor, and disease activity score based on a 28-joint count, reported Dr. Bøyesen of Diakonhjemmet Hospital, Oslo.

USGS inflammation was the best of 12 imaging modalities and measures of disease severity in identifying patients at risk of developing erosions on MRI, with a sensitivity of 78%, a specificity of 55%, a positive likelihood ration of 1.75, and accuracy of 70%.

Future studies are needed using composite indices of disease progression, including modern imaging modalities, to determine their value as predictors of an individual patient's likelihood of disease progression, the investigators concluded.

The study appears to be the first to confirm previous data suggesting that measuring inflammation by ultrasound can help predict subsequent joint damage, they noted. The findings also confirmed previous data identifying bone marrow edema on MRI as an independent predictor of joint damage.

Other imaging modalities in the study included digital x-ray radiogrammetry (DXR) of cortical bone mineral density in the hand. Results showed only trends toward higher levels of synovitis on MRI and bone density loss on DXR in patients with erosive progression of disease at 1 year. The findings did not support previous studies that reported cortical hand bone mineral density to be independently predictive of erosive progression, perhaps due to the small size of the study, Dr. Bøyesen added.

Given the comprehensive comparison of imaging modalities in the study, however, 84 patients can be considered a large number, the investigators noted.

The multivariate analyses controlled for the effects of age, sex, and other independent variables.

The investigators declared having no conflicts of interest. The study was funded by the Eastern Norway Regional Health Authority, the Research Council of Norway, the Norwegian Rheumatism Association, the Norwegian Women Public Health Association, the Grethe Harbitz Legacy, and the Marie and Else Mustad Legacy.

Baseline USGS (A) and 1-year MRI (B-D) of the radio-carpal joint are shown in a patient without erosive progression and in a patient with erosions (arrows) (E-H).

Source Courtesy Dr. Pernille Bøyesen