Rheumatoid Arthritis

Radiographs obtained of both hands showed similar changes in multiple phalanges. In particular, the lesions had a lacy, punched-out appearance that suggested osseous sarcoidosis, said Dr. Sterling G. West, a professor of medicine in the division of rheumatology at the University of Colorado at Denver.

The lesions reflect granulomatous involvement of the phalangeal shafts.

Notably, the lesions are not associated with periostitis or sequestra helping to separate sarcoid bone involvement from chronic osteomyelitis.

Sarcoidosis can have a number of manifestations, though pulmonary involvement is present in more than 90% of patients with the disease. Symptoms of pulmonary involvement include dyspnea and dry cough, as in this patient.

Patients tend to have well-established sarcoidosis by the time that bone involvement is present, said Dr. West. Bone involvement tends to occur more frequently in African Americans.

Cystic lesions have a predilection for the phalanges of the hands and feet. Soft tissue swelling can occur over the lesions. Sarcoidosis is the major cause of unidigital clubbing. When sarcoid bone involvement is associated with lupus pernio, the prognosis is generally poor.

Uveitis is another common manifestation of sarcoidosis and is usually bilateral. Dr. West recommends that all sarcoid patients get an eye screening.

Many patients with sarcoidosis undergo spontaneous remission, while some remit with steroids. Others may have a chronic course. Signs of poor prognosis include the involvement of three or more organs, disease onset after age 40, African American race, and symptoms lasting more than 6 months.

Osseous sarcoid typically indicates advanced sarcoidosis, which requires treatment with high-dose prednisone and additional agents such as azathioprine, methotrexate, or biologic agents—particularly infliximab to control all the sarcoidosis manifestations and prevent progression. This patient was initially treated with prednisone and azathioprine. Later, infliximab was added helping to stabilize his disease.

Osseous sarcoid lesions affected multiple phalanges (hand, above left). These bony changes typically have a lacy, punched-out appearance (detail, above right). Photos courtesy Dr. Sterling G. West

Radiographs obtained of both hands showed similar changes in multiple phalanges. In particular, the lesions had a lacy, punched-out appearance that suggested osseous sarcoidosis, said Dr. Sterling G. West, a professor of medicine in the division of rheumatology at the University of Colorado at Denver.

The lesions reflect granulomatous involvement of the phalangeal shafts.

Notably, the lesions are not associated with periostitis or sequestra helping to separate sarcoid bone involvement from chronic osteomyelitis.

Sarcoidosis can have a number of manifestations, though pulmonary involvement is present in more than 90% of patients with the disease. Symptoms of pulmonary involvement include dyspnea and dry cough, as in this patient.

Patients tend to have well-established sarcoidosis by the time that bone involvement is present, said Dr. West. Bone involvement tends to occur more frequently in African Americans.

Cystic lesions have a predilection for the phalanges of the hands and feet. Soft tissue swelling can occur over the lesions. Sarcoidosis is the major cause of unidigital clubbing. When sarcoid bone involvement is associated with lupus pernio, the prognosis is generally poor.

Uveitis is another common manifestation of sarcoidosis and is usually bilateral. Dr. West recommends that all sarcoid patients get an eye screening.

Many patients with sarcoidosis undergo spontaneous remission, while some remit with steroids. Others may have a chronic course. Signs of poor prognosis include the involvement of three or more organs, disease onset after age 40, African American race, and symptoms lasting more than 6 months.

Osseous sarcoid typically indicates advanced sarcoidosis, which requires treatment with high-dose prednisone and additional agents such as azathioprine, methotrexate, or biologic agents—particularly infliximab to control all the sarcoidosis manifestations and prevent progression. This patient was initially treated with prednisone and azathioprine. Later, infliximab was added helping to stabilize his disease.

Osseous sarcoid lesions affected multiple phalanges (hand, above left). These bony changes typically have a lacy, punched-out appearance (detail, above right). Photos courtesy Dr. Sterling G. West

Radiographs obtained of both hands showed similar changes in multiple phalanges. In particular, the lesions had a lacy, punched-out appearance that suggested osseous sarcoidosis, said Dr. Sterling G. West, a professor of medicine in the division of rheumatology at the University of Colorado at Denver.

The lesions reflect granulomatous involvement of the phalangeal shafts.

Notably, the lesions are not associated with periostitis or sequestra helping to separate sarcoid bone involvement from chronic osteomyelitis.

Sarcoidosis can have a number of manifestations, though pulmonary involvement is present in more than 90% of patients with the disease. Symptoms of pulmonary involvement include dyspnea and dry cough, as in this patient.

Patients tend to have well-established sarcoidosis by the time that bone involvement is present, said Dr. West. Bone involvement tends to occur more frequently in African Americans.

Cystic lesions have a predilection for the phalanges of the hands and feet. Soft tissue swelling can occur over the lesions. Sarcoidosis is the major cause of unidigital clubbing. When sarcoid bone involvement is associated with lupus pernio, the prognosis is generally poor.

Uveitis is another common manifestation of sarcoidosis and is usually bilateral. Dr. West recommends that all sarcoid patients get an eye screening.

Many patients with sarcoidosis undergo spontaneous remission, while some remit with steroids. Others may have a chronic course. Signs of poor prognosis include the involvement of three or more organs, disease onset after age 40, African American race, and symptoms lasting more than 6 months.

Osseous sarcoid typically indicates advanced sarcoidosis, which requires treatment with high-dose prednisone and additional agents such as azathioprine, methotrexate, or biologic agents—particularly infliximab to control all the sarcoidosis manifestations and prevent progression. This patient was initially treated with prednisone and azathioprine. Later, infliximab was added helping to stabilize his disease.

Osseous sarcoid lesions affected multiple phalanges (hand, above left). These bony changes typically have a lacy, punched-out appearance (detail, above right). Photos courtesy Dr. Sterling G. West

The absence of large joint involvement, higher serum C-reactive protein levels, and lower disability scores at treatment initiation may be predictors of a good therapeutic response to infliximab in refractory psoriatic polyarthritis, an open-label study has shown.

The efficacy of infliximab in psoriatic arthritis patients has been demonstrated in several placebo controlled and open label trials, but the high cost and potential risks associated with the anti-tumor necrosis factor-α (TNF-α) agent warrants careful selection of patients who are most likely to benefit from this treatment, wrote Dr. Jordi Gratacós of Parc Taulí University Hospital in Barcelona, and colleagues.

To this end, the investigators sought to identify variables associated with a good clinical response in psoriatic arthritis patients being treated with the drug (Ann. Rheum. Dis. 2007 Jan. 25 [Epub doi: 10.1136/ard.2006.060079]).

The multicenter study included 69 patients with active psoriatic arthritis who showed no clinically significant response to at least 8 weeks of treatment with 15 mg of methotrexate weekly. Per study criteria, patients had to have peripheral polyarthritis—defined by the presence of five or more swollen and tender joints—and at least one of the following criteria: morning stiffness lasting more than 45 minutes, an erythrocyte sedimentation rate (ESR) of more than 30 mm per first hour, or a C-reactive protein (CRP) level greater than 15 mg/L. Patients testing positive for rheumatoid factor were excluded from the investigation.

In addition to their stable doses of methotrexate, study participants received 5mg/kg of inifliximab every 8 weeks.

In an intent-to-treat analysis conducted at 38 weeks of active treatment, 30 of the 69 patients (44%) experienced a major clinical response, defined as an improvement of at least 50% of the initial American College of Rheumatology (ACR) composite index, the authors reported. With use of the ACR20 and ACR70 measures, 44 and 18 patients, respectively, were identified as responders.

The results of a univariate analysis based on an ACR50 response at 38 weeks as the main outcome showed that involvement of large joints (hip or knee) and a high level of disability, defined as a score of 2 or higher on the validated Health Assessment Questionnaire (HAQ) at the start of treatment “were both predictors of smaller response to infliximab than in patients with no involvement of the large joints and an HAQ less than 2,” the authors wrote.

When the univariate analysis was performed at 14 weeks, the results were similar except for associations with CRP and age.

In the 14-week analysis, the presence of a CRP of at least 10 mg/L at the start of treatment “was associated with a significantly high rate of response,” reported the authors. And patients who achieved an ACR50 were younger (mean age 39 years), compared with those who did not respond (mean age 45 years), they wrote.

In a multivariate logistic regression model, CRP values and the absence of arthritis in the hip or knee or both were independent predictors of an ACR50 response.

Severe disability was not a significant predictor, but there was a trend toward an association, the authors reported.

While the results of this study suggest that some variables may significantly influence the treatment response to infliximab among patients with psoriatic arthritis, “the data reported here cannot be used as a definitive guide for deciding which patients should be given anti-TNF treatment,” the authors stressed, noting the study's small size and focus on patients with the most severe and refractory disease usually seen in clinical practice. “Large studies supporting our data will be needed in order to prove our statistical model and to establish more accurately the predictive factors for clinical response to infliximab in patients with [psoriatic arthritis],” they concluded.

The absence of large joint involvement, higher serum C-reactive protein levels, and lower disability scores at treatment initiation may be predictors of a good therapeutic response to infliximab in refractory psoriatic polyarthritis, an open-label study has shown.

The efficacy of infliximab in psoriatic arthritis patients has been demonstrated in several placebo controlled and open label trials, but the high cost and potential risks associated with the anti-tumor necrosis factor-α (TNF-α) agent warrants careful selection of patients who are most likely to benefit from this treatment, wrote Dr. Jordi Gratacós of Parc Taulí University Hospital in Barcelona, and colleagues.

To this end, the investigators sought to identify variables associated with a good clinical response in psoriatic arthritis patients being treated with the drug (Ann. Rheum. Dis. 2007 Jan. 25 [Epub doi: 10.1136/ard.2006.060079]).

The multicenter study included 69 patients with active psoriatic arthritis who showed no clinically significant response to at least 8 weeks of treatment with 15 mg of methotrexate weekly. Per study criteria, patients had to have peripheral polyarthritis—defined by the presence of five or more swollen and tender joints—and at least one of the following criteria: morning stiffness lasting more than 45 minutes, an erythrocyte sedimentation rate (ESR) of more than 30 mm per first hour, or a C-reactive protein (CRP) level greater than 15 mg/L. Patients testing positive for rheumatoid factor were excluded from the investigation.

In addition to their stable doses of methotrexate, study participants received 5mg/kg of inifliximab every 8 weeks.

In an intent-to-treat analysis conducted at 38 weeks of active treatment, 30 of the 69 patients (44%) experienced a major clinical response, defined as an improvement of at least 50% of the initial American College of Rheumatology (ACR) composite index, the authors reported. With use of the ACR20 and ACR70 measures, 44 and 18 patients, respectively, were identified as responders.

The results of a univariate analysis based on an ACR50 response at 38 weeks as the main outcome showed that involvement of large joints (hip or knee) and a high level of disability, defined as a score of 2 or higher on the validated Health Assessment Questionnaire (HAQ) at the start of treatment “were both predictors of smaller response to infliximab than in patients with no involvement of the large joints and an HAQ less than 2,” the authors wrote.

When the univariate analysis was performed at 14 weeks, the results were similar except for associations with CRP and age.

In the 14-week analysis, the presence of a CRP of at least 10 mg/L at the start of treatment “was associated with a significantly high rate of response,” reported the authors. And patients who achieved an ACR50 were younger (mean age 39 years), compared with those who did not respond (mean age 45 years), they wrote.

In a multivariate logistic regression model, CRP values and the absence of arthritis in the hip or knee or both were independent predictors of an ACR50 response.

Severe disability was not a significant predictor, but there was a trend toward an association, the authors reported.

While the results of this study suggest that some variables may significantly influence the treatment response to infliximab among patients with psoriatic arthritis, “the data reported here cannot be used as a definitive guide for deciding which patients should be given anti-TNF treatment,” the authors stressed, noting the study's small size and focus on patients with the most severe and refractory disease usually seen in clinical practice. “Large studies supporting our data will be needed in order to prove our statistical model and to establish more accurately the predictive factors for clinical response to infliximab in patients with [psoriatic arthritis],” they concluded.

The absence of large joint involvement, higher serum C-reactive protein levels, and lower disability scores at treatment initiation may be predictors of a good therapeutic response to infliximab in refractory psoriatic polyarthritis, an open-label study has shown.

The efficacy of infliximab in psoriatic arthritis patients has been demonstrated in several placebo controlled and open label trials, but the high cost and potential risks associated with the anti-tumor necrosis factor-α (TNF-α) agent warrants careful selection of patients who are most likely to benefit from this treatment, wrote Dr. Jordi Gratacós of Parc Taulí University Hospital in Barcelona, and colleagues.

To this end, the investigators sought to identify variables associated with a good clinical response in psoriatic arthritis patients being treated with the drug (Ann. Rheum. Dis. 2007 Jan. 25 [Epub doi: 10.1136/ard.2006.060079]).

The multicenter study included 69 patients with active psoriatic arthritis who showed no clinically significant response to at least 8 weeks of treatment with 15 mg of methotrexate weekly. Per study criteria, patients had to have peripheral polyarthritis—defined by the presence of five or more swollen and tender joints—and at least one of the following criteria: morning stiffness lasting more than 45 minutes, an erythrocyte sedimentation rate (ESR) of more than 30 mm per first hour, or a C-reactive protein (CRP) level greater than 15 mg/L. Patients testing positive for rheumatoid factor were excluded from the investigation.

In addition to their stable doses of methotrexate, study participants received 5mg/kg of inifliximab every 8 weeks.

In an intent-to-treat analysis conducted at 38 weeks of active treatment, 30 of the 69 patients (44%) experienced a major clinical response, defined as an improvement of at least 50% of the initial American College of Rheumatology (ACR) composite index, the authors reported. With use of the ACR20 and ACR70 measures, 44 and 18 patients, respectively, were identified as responders.

The results of a univariate analysis based on an ACR50 response at 38 weeks as the main outcome showed that involvement of large joints (hip or knee) and a high level of disability, defined as a score of 2 or higher on the validated Health Assessment Questionnaire (HAQ) at the start of treatment “were both predictors of smaller response to infliximab than in patients with no involvement of the large joints and an HAQ less than 2,” the authors wrote.

When the univariate analysis was performed at 14 weeks, the results were similar except for associations with CRP and age.

In the 14-week analysis, the presence of a CRP of at least 10 mg/L at the start of treatment “was associated with a significantly high rate of response,” reported the authors. And patients who achieved an ACR50 were younger (mean age 39 years), compared with those who did not respond (mean age 45 years), they wrote.

In a multivariate logistic regression model, CRP values and the absence of arthritis in the hip or knee or both were independent predictors of an ACR50 response.

Severe disability was not a significant predictor, but there was a trend toward an association, the authors reported.

While the results of this study suggest that some variables may significantly influence the treatment response to infliximab among patients with psoriatic arthritis, “the data reported here cannot be used as a definitive guide for deciding which patients should be given anti-TNF treatment,” the authors stressed, noting the study's small size and focus on patients with the most severe and refractory disease usually seen in clinical practice. “Large studies supporting our data will be needed in order to prove our statistical model and to establish more accurately the predictive factors for clinical response to infliximab in patients with [psoriatic arthritis],” they concluded.

The cyclooxygenase-2 inhibitor etoricoxib caused fewer clinically important upper GI events than the traditional NSAID diclofenac in a large study designed to reflect the real-world experience of treating osteoarthritis and rheumatoid arthritis.

The Multinational Etoricoxib and Diclofenac Arthritis Long-Term Program (MEDAL) pooled the results of three large randomized clinical trials involving nearly 35,000 patients treated at 1,380 sites in 46 countries. Unlike in most clinical trials, subjects in the MEDAL program were encouraged to use proton pump inhibitor therapy to protect against GI damage, and those at cardiovascular risk were encouraged to add low-dose aspirin to their regimens, investigators reported.

Etoricoxib and diclofenac had similar efficacy against arthritis. Upper GI events, primarily uncomplicated ulcers, were significantly less frequent with etoricoxib than with diclofenac. There was no difference between the two drugs in rates of more serious complicated events, reported Dr. Loren Laine and associates in the MEDAL program (Lancet 2007;369:465–73).

Significantly fewer patients taking etoricoxib discontinued treatment because of dyspepsia, compared with those taking diclofenac.

This study was sponsored by Merck Research Laboratories, which conducted the statistical analyses and was involved in data analysis, safety monitoring, and reporting.

The cyclooxygenase-2 inhibitor etoricoxib caused fewer clinically important upper GI events than the traditional NSAID diclofenac in a large study designed to reflect the real-world experience of treating osteoarthritis and rheumatoid arthritis.

The Multinational Etoricoxib and Diclofenac Arthritis Long-Term Program (MEDAL) pooled the results of three large randomized clinical trials involving nearly 35,000 patients treated at 1,380 sites in 46 countries. Unlike in most clinical trials, subjects in the MEDAL program were encouraged to use proton pump inhibitor therapy to protect against GI damage, and those at cardiovascular risk were encouraged to add low-dose aspirin to their regimens, investigators reported.

Etoricoxib and diclofenac had similar efficacy against arthritis. Upper GI events, primarily uncomplicated ulcers, were significantly less frequent with etoricoxib than with diclofenac. There was no difference between the two drugs in rates of more serious complicated events, reported Dr. Loren Laine and associates in the MEDAL program (Lancet 2007;369:465–73).

Significantly fewer patients taking etoricoxib discontinued treatment because of dyspepsia, compared with those taking diclofenac.

This study was sponsored by Merck Research Laboratories, which conducted the statistical analyses and was involved in data analysis, safety monitoring, and reporting.

The cyclooxygenase-2 inhibitor etoricoxib caused fewer clinically important upper GI events than the traditional NSAID diclofenac in a large study designed to reflect the real-world experience of treating osteoarthritis and rheumatoid arthritis.

The Multinational Etoricoxib and Diclofenac Arthritis Long-Term Program (MEDAL) pooled the results of three large randomized clinical trials involving nearly 35,000 patients treated at 1,380 sites in 46 countries. Unlike in most clinical trials, subjects in the MEDAL program were encouraged to use proton pump inhibitor therapy to protect against GI damage, and those at cardiovascular risk were encouraged to add low-dose aspirin to their regimens, investigators reported.

Etoricoxib and diclofenac had similar efficacy against arthritis. Upper GI events, primarily uncomplicated ulcers, were significantly less frequent with etoricoxib than with diclofenac. There was no difference between the two drugs in rates of more serious complicated events, reported Dr. Loren Laine and associates in the MEDAL program (Lancet 2007;369:465–73).

Significantly fewer patients taking etoricoxib discontinued treatment because of dyspepsia, compared with those taking diclofenac.

This study was sponsored by Merck Research Laboratories, which conducted the statistical analyses and was involved in data analysis, safety monitoring, and reporting.

Cigarette smoking does not appear to negatively influence the progression of radiographic damage in rheumatoid arthritis, a prospective study has shown. In fact, radiographic progression of disease was significantly less among heavy smokers than among moderate smokers and nonsmokers in the longitudinal observational investigation of rheumatoid arthritis patients.

Because smoking is an established risk factor for the development of rheumatoid arthritis (RA), investigators with the Swiss Clinical Quality Management (SCQM) project for RA—a population-based registry designed to monitor disease activity—hypothesized that smoking would exacerbate disease progression. Yet, a comparison of smokers and nonsmokers from the registry showed that radiographic joint damage progressed at an equivalent rate in both groups, reported Dr. Axel Finckh of the Geneva University Hospital and colleagues. “Furthermore, we observed a significant trend for reduced radiographic progression and generally more favorable functional scores among heavy smokers, suggesting that cigarette smoke does not accelerate RA disease progress,” the authors wrote (Ann. Rheum. Dis. 2007 [Epub doi: 10.1136/ard.2006.065060]).

The SCQM system requests at least yearly assessments of disease activity, radiographic damage, antirheumatic therapy, sociodemographic factors, and lifestyle characteristics, including cigarette-smoking history. The cohort for the current study included 2,004 registry patients for whom cigarette smoking history and at least two consecutive sets of radiographs were available.

Progression of radiographic joint damage, as measured by changes from baseline in radiographic damage scores, was the study's primary outcome, and the progression of functional disability as measured by change from baseline in the Stanford Health Assessment Questionnaire (HAQ) disability index was the secondary outcome. The outcome analyses included data collected between March 1996 and November 2005.

Of the 2,004 patients eligible for study inclusion, 545 were current smokers consuming, on average 16 cigarettes per day, with a mean past smoking exposure of 20.6 pack-years. Of the 545 smokers, 55 were characterized as heavy smokers with a reported average intake of 33 cigarettes per day and 27.7 years of smoking and 489 met the criteria for moderate smokers, with an average of 13 cigarettes per day and 24.2 years of smoking.

The smokers were predominantly younger males with shorter disease durations and less joint erosions at baseline, the authors reported. There were no significant differences between smokers and nonsmokers with respect to other important risk factors for disease progression, such as rheumatoid factor seropositivity, antirheumatic therapy, glucocorticoid use, functional status, and educational level.

In both crude and adjusted models of radiographic progression, there was no evidence for more rapid progression among smokers than nonsmokers, according to the authors. “In the fully adjusted model, radiographic damage progressed by 2.79% at 2 years in nonsmokers compared to 2.51% in smokers.”

There was an inverse dose-response effect for heavy smokers, compared with moderate smokers and nonsmokers. “Specifically, radiographic erosions evolved significantly more slowly in heavy smokers [average 1.21% in 2 years] compared to nonsmokers [2.86%], whereas erosive disease in moderate smokers [2.71%] progressed at a rate similar to that in nonsmokers,” the authors reported.

A sensitivity analysis examining current smoking exposure as a continuous variable and with an alternative categorization demonstrated a similar inverse dose-response effect as did analyses restricted to subgroups of patients with rheumatoid factor-positive disease, male patients, and patients treated with tumor necrosis factor inhibitors, according to the authors, who noted that “the strongest predictors of radiographic damage progression were disease duration, baseline radiographic damage, and rheumatoid factor.”

With respect to functional disability, “overall, mean HAQ scores tended to improve somewhat during the first years of the observation,” the authors reported, linking the improvements to the initiation of new antirheumatic therapies at the time of enrollment.

As for functional capacity relative to smoking status, “the evolution of HAQ scores did not differ significantly between smokers and nonsmokers,” the authors wrote, nor was there a significant inverse dose-response effect in heavy smokers, compared with moderate smokers and nonsmokers. High baseline HAQ score, female gender, rheumatoid factor, and lower educational levels were strong predictors for functional disability.

The results of this study suggest, “that smoking may be more important in the initiation of RA than in the perpetuation of the erosive disease process,” the authors noted.

Previous studies have shown some protective effects of smoking in several inflammatory diseases, and nicotine specifically has been shown to have anti-inflammatory properties, which may support the current findings in RA patients, the authors wrote. Smoking or nicotine exposure should not be a therapeutic consideration. “Global health risks associated with smoking are much greater than those potential benefits,” they said.

The exclusion from the study of registry patients with no radiographic follow-up could potentially contribute to a selection bias, although there is no indication that the missing radiographic follow-up was associated with smoking and more severe radiographic progression, the authors wrote.

Cigarette smoking does not appear to negatively influence the progression of radiographic damage in rheumatoid arthritis, a prospective study has shown. In fact, radiographic progression of disease was significantly less among heavy smokers than among moderate smokers and nonsmokers in the longitudinal observational investigation of rheumatoid arthritis patients.

Because smoking is an established risk factor for the development of rheumatoid arthritis (RA), investigators with the Swiss Clinical Quality Management (SCQM) project for RA—a population-based registry designed to monitor disease activity—hypothesized that smoking would exacerbate disease progression. Yet, a comparison of smokers and nonsmokers from the registry showed that radiographic joint damage progressed at an equivalent rate in both groups, reported Dr. Axel Finckh of the Geneva University Hospital and colleagues. “Furthermore, we observed a significant trend for reduced radiographic progression and generally more favorable functional scores among heavy smokers, suggesting that cigarette smoke does not accelerate RA disease progress,” the authors wrote (Ann. Rheum. Dis. 2007 [Epub doi: 10.1136/ard.2006.065060]).

The SCQM system requests at least yearly assessments of disease activity, radiographic damage, antirheumatic therapy, sociodemographic factors, and lifestyle characteristics, including cigarette-smoking history. The cohort for the current study included 2,004 registry patients for whom cigarette smoking history and at least two consecutive sets of radiographs were available.

Progression of radiographic joint damage, as measured by changes from baseline in radiographic damage scores, was the study's primary outcome, and the progression of functional disability as measured by change from baseline in the Stanford Health Assessment Questionnaire (HAQ) disability index was the secondary outcome. The outcome analyses included data collected between March 1996 and November 2005.

Of the 2,004 patients eligible for study inclusion, 545 were current smokers consuming, on average 16 cigarettes per day, with a mean past smoking exposure of 20.6 pack-years. Of the 545 smokers, 55 were characterized as heavy smokers with a reported average intake of 33 cigarettes per day and 27.7 years of smoking and 489 met the criteria for moderate smokers, with an average of 13 cigarettes per day and 24.2 years of smoking.

The smokers were predominantly younger males with shorter disease durations and less joint erosions at baseline, the authors reported. There were no significant differences between smokers and nonsmokers with respect to other important risk factors for disease progression, such as rheumatoid factor seropositivity, antirheumatic therapy, glucocorticoid use, functional status, and educational level.

In both crude and adjusted models of radiographic progression, there was no evidence for more rapid progression among smokers than nonsmokers, according to the authors. “In the fully adjusted model, radiographic damage progressed by 2.79% at 2 years in nonsmokers compared to 2.51% in smokers.”

There was an inverse dose-response effect for heavy smokers, compared with moderate smokers and nonsmokers. “Specifically, radiographic erosions evolved significantly more slowly in heavy smokers [average 1.21% in 2 years] compared to nonsmokers [2.86%], whereas erosive disease in moderate smokers [2.71%] progressed at a rate similar to that in nonsmokers,” the authors reported.

A sensitivity analysis examining current smoking exposure as a continuous variable and with an alternative categorization demonstrated a similar inverse dose-response effect as did analyses restricted to subgroups of patients with rheumatoid factor-positive disease, male patients, and patients treated with tumor necrosis factor inhibitors, according to the authors, who noted that “the strongest predictors of radiographic damage progression were disease duration, baseline radiographic damage, and rheumatoid factor.”

With respect to functional disability, “overall, mean HAQ scores tended to improve somewhat during the first years of the observation,” the authors reported, linking the improvements to the initiation of new antirheumatic therapies at the time of enrollment.

As for functional capacity relative to smoking status, “the evolution of HAQ scores did not differ significantly between smokers and nonsmokers,” the authors wrote, nor was there a significant inverse dose-response effect in heavy smokers, compared with moderate smokers and nonsmokers. High baseline HAQ score, female gender, rheumatoid factor, and lower educational levels were strong predictors for functional disability.

The results of this study suggest, “that smoking may be more important in the initiation of RA than in the perpetuation of the erosive disease process,” the authors noted.

Previous studies have shown some protective effects of smoking in several inflammatory diseases, and nicotine specifically has been shown to have anti-inflammatory properties, which may support the current findings in RA patients, the authors wrote. Smoking or nicotine exposure should not be a therapeutic consideration. “Global health risks associated with smoking are much greater than those potential benefits,” they said.

The exclusion from the study of registry patients with no radiographic follow-up could potentially contribute to a selection bias, although there is no indication that the missing radiographic follow-up was associated with smoking and more severe radiographic progression, the authors wrote.

Cigarette smoking does not appear to negatively influence the progression of radiographic damage in rheumatoid arthritis, a prospective study has shown. In fact, radiographic progression of disease was significantly less among heavy smokers than among moderate smokers and nonsmokers in the longitudinal observational investigation of rheumatoid arthritis patients.

Because smoking is an established risk factor for the development of rheumatoid arthritis (RA), investigators with the Swiss Clinical Quality Management (SCQM) project for RA—a population-based registry designed to monitor disease activity—hypothesized that smoking would exacerbate disease progression. Yet, a comparison of smokers and nonsmokers from the registry showed that radiographic joint damage progressed at an equivalent rate in both groups, reported Dr. Axel Finckh of the Geneva University Hospital and colleagues. “Furthermore, we observed a significant trend for reduced radiographic progression and generally more favorable functional scores among heavy smokers, suggesting that cigarette smoke does not accelerate RA disease progress,” the authors wrote (Ann. Rheum. Dis. 2007 [Epub doi: 10.1136/ard.2006.065060]).

The SCQM system requests at least yearly assessments of disease activity, radiographic damage, antirheumatic therapy, sociodemographic factors, and lifestyle characteristics, including cigarette-smoking history. The cohort for the current study included 2,004 registry patients for whom cigarette smoking history and at least two consecutive sets of radiographs were available.

Progression of radiographic joint damage, as measured by changes from baseline in radiographic damage scores, was the study's primary outcome, and the progression of functional disability as measured by change from baseline in the Stanford Health Assessment Questionnaire (HAQ) disability index was the secondary outcome. The outcome analyses included data collected between March 1996 and November 2005.

Of the 2,004 patients eligible for study inclusion, 545 were current smokers consuming, on average 16 cigarettes per day, with a mean past smoking exposure of 20.6 pack-years. Of the 545 smokers, 55 were characterized as heavy smokers with a reported average intake of 33 cigarettes per day and 27.7 years of smoking and 489 met the criteria for moderate smokers, with an average of 13 cigarettes per day and 24.2 years of smoking.

The smokers were predominantly younger males with shorter disease durations and less joint erosions at baseline, the authors reported. There were no significant differences between smokers and nonsmokers with respect to other important risk factors for disease progression, such as rheumatoid factor seropositivity, antirheumatic therapy, glucocorticoid use, functional status, and educational level.

In both crude and adjusted models of radiographic progression, there was no evidence for more rapid progression among smokers than nonsmokers, according to the authors. “In the fully adjusted model, radiographic damage progressed by 2.79% at 2 years in nonsmokers compared to 2.51% in smokers.”

There was an inverse dose-response effect for heavy smokers, compared with moderate smokers and nonsmokers. “Specifically, radiographic erosions evolved significantly more slowly in heavy smokers [average 1.21% in 2 years] compared to nonsmokers [2.86%], whereas erosive disease in moderate smokers [2.71%] progressed at a rate similar to that in nonsmokers,” the authors reported.

A sensitivity analysis examining current smoking exposure as a continuous variable and with an alternative categorization demonstrated a similar inverse dose-response effect as did analyses restricted to subgroups of patients with rheumatoid factor-positive disease, male patients, and patients treated with tumor necrosis factor inhibitors, according to the authors, who noted that “the strongest predictors of radiographic damage progression were disease duration, baseline radiographic damage, and rheumatoid factor.”

With respect to functional disability, “overall, mean HAQ scores tended to improve somewhat during the first years of the observation,” the authors reported, linking the improvements to the initiation of new antirheumatic therapies at the time of enrollment.

As for functional capacity relative to smoking status, “the evolution of HAQ scores did not differ significantly between smokers and nonsmokers,” the authors wrote, nor was there a significant inverse dose-response effect in heavy smokers, compared with moderate smokers and nonsmokers. High baseline HAQ score, female gender, rheumatoid factor, and lower educational levels were strong predictors for functional disability.

The results of this study suggest, “that smoking may be more important in the initiation of RA than in the perpetuation of the erosive disease process,” the authors noted.

Previous studies have shown some protective effects of smoking in several inflammatory diseases, and nicotine specifically has been shown to have anti-inflammatory properties, which may support the current findings in RA patients, the authors wrote. Smoking or nicotine exposure should not be a therapeutic consideration. “Global health risks associated with smoking are much greater than those potential benefits,” they said.

The exclusion from the study of registry patients with no radiographic follow-up could potentially contribute to a selection bias, although there is no indication that the missing radiographic follow-up was associated with smoking and more severe radiographic progression, the authors wrote.

PRAGUE — Nonpharmacologic therapies remain less commonly prescribed than are pharmacologic therapies for the treatment of knee and hand osteoarthritis—and this trend has been noted both for primary care physicians and rheumatologists, according to two studies presented at the 2006 World Congress on Osteoarthritis.

When it comes to primary care physicians (PCPs) treating knee osteoarthritis (OA), nonpharmacologic treatments are “insufficiently prescribed and, when initiated, are rarely continued over the long term,” reported Dr. Bernard Mazières of Rangueil University Hospital, in Toulouse, France. However, first-line pharmacologic treatment with acetaminophen was initiated in 96% of patients, Dr. Mazières reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Dr. Mazières' observational, prospective, multicenter, 1-year cohort study included a total of 933 knee OA patients from 383 randomly selected PCPs in France and Spain. Information on the EULAR recommendations for treating knee OA was provided to the PCPs at the start of the study.

While 99% of the patients were prescribed acetaminophen during the study period, only 47% (437) were prescribed a treatment strictly following the EULAR recommendations. Among those who received nonpharmacologic therapy, the most common prescription was rehabilitation (40%), followed by weight loss (24%), and education (20%). The study concluded that under these therapeutic conditions patients were satisfied with their OA treatment and “improvement in pain, stiffness, and clinical signs of inflammation was clinically relevant.”

In a separate oral presentation at the meeting, Dr. Emmanuel Maheu reported that, when compared with PCPs, rheumatologists are no better at prescribing nonpharmacologic therapy—at least when it comes to the treatment of hand osteoarthritis.

His prospective cross-sectional study included 169 French rheumatologists and PCPs treating 316 hand OA patients. The study found that, when compared with rheumatologists, PCPs prescribed more analgesics (93% vs. 73%), more nonsteroidal anti-inflammatories (62% vs. 43%), and “surprisingly” more physical therapy (19% vs. 3%), said Dr. Maheu, of St. Antoine Hospital, Paris.

Rheumatologists prescribed more splints (30% vs. 13%) and more intra-articular steroid injections (16% vs. 5%).

PRAGUE — Nonpharmacologic therapies remain less commonly prescribed than are pharmacologic therapies for the treatment of knee and hand osteoarthritis—and this trend has been noted both for primary care physicians and rheumatologists, according to two studies presented at the 2006 World Congress on Osteoarthritis.

When it comes to primary care physicians (PCPs) treating knee osteoarthritis (OA), nonpharmacologic treatments are “insufficiently prescribed and, when initiated, are rarely continued over the long term,” reported Dr. Bernard Mazières of Rangueil University Hospital, in Toulouse, France. However, first-line pharmacologic treatment with acetaminophen was initiated in 96% of patients, Dr. Mazières reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Dr. Mazières' observational, prospective, multicenter, 1-year cohort study included a total of 933 knee OA patients from 383 randomly selected PCPs in France and Spain. Information on the EULAR recommendations for treating knee OA was provided to the PCPs at the start of the study.

While 99% of the patients were prescribed acetaminophen during the study period, only 47% (437) were prescribed a treatment strictly following the EULAR recommendations. Among those who received nonpharmacologic therapy, the most common prescription was rehabilitation (40%), followed by weight loss (24%), and education (20%). The study concluded that under these therapeutic conditions patients were satisfied with their OA treatment and “improvement in pain, stiffness, and clinical signs of inflammation was clinically relevant.”

In a separate oral presentation at the meeting, Dr. Emmanuel Maheu reported that, when compared with PCPs, rheumatologists are no better at prescribing nonpharmacologic therapy—at least when it comes to the treatment of hand osteoarthritis.

His prospective cross-sectional study included 169 French rheumatologists and PCPs treating 316 hand OA patients. The study found that, when compared with rheumatologists, PCPs prescribed more analgesics (93% vs. 73%), more nonsteroidal anti-inflammatories (62% vs. 43%), and “surprisingly” more physical therapy (19% vs. 3%), said Dr. Maheu, of St. Antoine Hospital, Paris.

Rheumatologists prescribed more splints (30% vs. 13%) and more intra-articular steroid injections (16% vs. 5%).

PRAGUE — Nonpharmacologic therapies remain less commonly prescribed than are pharmacologic therapies for the treatment of knee and hand osteoarthritis—and this trend has been noted both for primary care physicians and rheumatologists, according to two studies presented at the 2006 World Congress on Osteoarthritis.

When it comes to primary care physicians (PCPs) treating knee osteoarthritis (OA), nonpharmacologic treatments are “insufficiently prescribed and, when initiated, are rarely continued over the long term,” reported Dr. Bernard Mazières of Rangueil University Hospital, in Toulouse, France. However, first-line pharmacologic treatment with acetaminophen was initiated in 96% of patients, Dr. Mazières reported at the meeting, which was sponsored by the Osteoarthritis Research Society International.

Dr. Mazières' observational, prospective, multicenter, 1-year cohort study included a total of 933 knee OA patients from 383 randomly selected PCPs in France and Spain. Information on the EULAR recommendations for treating knee OA was provided to the PCPs at the start of the study.

While 99% of the patients were prescribed acetaminophen during the study period, only 47% (437) were prescribed a treatment strictly following the EULAR recommendations. Among those who received nonpharmacologic therapy, the most common prescription was rehabilitation (40%), followed by weight loss (24%), and education (20%). The study concluded that under these therapeutic conditions patients were satisfied with their OA treatment and “improvement in pain, stiffness, and clinical signs of inflammation was clinically relevant.”

In a separate oral presentation at the meeting, Dr. Emmanuel Maheu reported that, when compared with PCPs, rheumatologists are no better at prescribing nonpharmacologic therapy—at least when it comes to the treatment of hand osteoarthritis.

His prospective cross-sectional study included 169 French rheumatologists and PCPs treating 316 hand OA patients. The study found that, when compared with rheumatologists, PCPs prescribed more analgesics (93% vs. 73%), more nonsteroidal anti-inflammatories (62% vs. 43%), and “surprisingly” more physical therapy (19% vs. 3%), said Dr. Maheu, of St. Antoine Hospital, Paris.

Rheumatologists prescribed more splints (30% vs. 13%) and more intra-articular steroid injections (16% vs. 5%).

Early functional disability independently predicted cardiovascular disease-related mortality as well as all-cause mortality in patients with inflammatory polyarthritis, investigators reported.

The finding builds on other studies demonstrating the predictive value of early functional disability in rheumatoid arthritis (RA), and “may help guide the targeting of aggressive therapies,” reported Tracey M. Farragher of the University of Manchester (England), and associates.

The investigators used the Norfolk Arthritis Register, in Norwich, England, to determine if early functional disability is a useful independent predictor of increased cardiac risk.

Disability was measured at baseline and again at 1 year using the Health Assessment Questionnaire (HAQ).

Patients were referred to the registry if they had swelling of at least two joints for at least 4 weeks. About 45% were classified as having RA at referral, and by 5 years about 67% had satisfied the American College of Rheumatology criteria for RA. All patients (mean age 54 years) were followed until death or for 10 years after registration, whichever came first.

By 10 years, 171 (17%) of 1,010 patients had died, and 89 (52%) of those deaths were attributed to cardiovascular disease.

Both all-cause mortality and cardiovascular disease-related mortality increased sharply as the HAQ scores from either the baseline assessment or the 1-year follow-up increased, the investigators reported (Ann. Rheum. Dis. 2006 Nov. 7 [Epub doi: 10.1136/ard.2006.056390]).

When year 1 HAQ scores were focused on and adjusted for other predictors, the investigators found that functional disability and rheumatoid factor positivity were independent predictors of subsequent early death, including cardiac death, according to the investigators. With each one-point increase in HAQ score, patients had a 48% higher risk of dying within the follow-up period, and a 52% higher risk of dying from cardiovascular disease.

Using HAQ scores obtained at baseline, the investigators found that while disability was a significant risk factor (increasing the risk of all-cause death and cardiovascular disease death by 27% and 15%, respectively, for each 1-point increase in HAQ score), rheumatoid factor positivity was the only independent predictor of all-cause and cardiovascular disease mortality. The investigators repeated the analysis for patients who satisfied ACR criteria for RA by 5 years, and found that the predictive value of 1-year HAQ scores was similar to the predictive value for patients with inflammatory polyarthritis and not RA.

Early functional disability independently predicted cardiovascular disease-related mortality as well as all-cause mortality in patients with inflammatory polyarthritis, investigators reported.

The finding builds on other studies demonstrating the predictive value of early functional disability in rheumatoid arthritis (RA), and “may help guide the targeting of aggressive therapies,” reported Tracey M. Farragher of the University of Manchester (England), and associates.

The investigators used the Norfolk Arthritis Register, in Norwich, England, to determine if early functional disability is a useful independent predictor of increased cardiac risk.

Disability was measured at baseline and again at 1 year using the Health Assessment Questionnaire (HAQ).

Patients were referred to the registry if they had swelling of at least two joints for at least 4 weeks. About 45% were classified as having RA at referral, and by 5 years about 67% had satisfied the American College of Rheumatology criteria for RA. All patients (mean age 54 years) were followed until death or for 10 years after registration, whichever came first.

By 10 years, 171 (17%) of 1,010 patients had died, and 89 (52%) of those deaths were attributed to cardiovascular disease.

Both all-cause mortality and cardiovascular disease-related mortality increased sharply as the HAQ scores from either the baseline assessment or the 1-year follow-up increased, the investigators reported (Ann. Rheum. Dis. 2006 Nov. 7 [Epub doi: 10.1136/ard.2006.056390]).

When year 1 HAQ scores were focused on and adjusted for other predictors, the investigators found that functional disability and rheumatoid factor positivity were independent predictors of subsequent early death, including cardiac death, according to the investigators. With each one-point increase in HAQ score, patients had a 48% higher risk of dying within the follow-up period, and a 52% higher risk of dying from cardiovascular disease.

Using HAQ scores obtained at baseline, the investigators found that while disability was a significant risk factor (increasing the risk of all-cause death and cardiovascular disease death by 27% and 15%, respectively, for each 1-point increase in HAQ score), rheumatoid factor positivity was the only independent predictor of all-cause and cardiovascular disease mortality. The investigators repeated the analysis for patients who satisfied ACR criteria for RA by 5 years, and found that the predictive value of 1-year HAQ scores was similar to the predictive value for patients with inflammatory polyarthritis and not RA.

Early functional disability independently predicted cardiovascular disease-related mortality as well as all-cause mortality in patients with inflammatory polyarthritis, investigators reported.

The finding builds on other studies demonstrating the predictive value of early functional disability in rheumatoid arthritis (RA), and “may help guide the targeting of aggressive therapies,” reported Tracey M. Farragher of the University of Manchester (England), and associates.

The investigators used the Norfolk Arthritis Register, in Norwich, England, to determine if early functional disability is a useful independent predictor of increased cardiac risk.

Disability was measured at baseline and again at 1 year using the Health Assessment Questionnaire (HAQ).

Patients were referred to the registry if they had swelling of at least two joints for at least 4 weeks. About 45% were classified as having RA at referral, and by 5 years about 67% had satisfied the American College of Rheumatology criteria for RA. All patients (mean age 54 years) were followed until death or for 10 years after registration, whichever came first.

By 10 years, 171 (17%) of 1,010 patients had died, and 89 (52%) of those deaths were attributed to cardiovascular disease.

Both all-cause mortality and cardiovascular disease-related mortality increased sharply as the HAQ scores from either the baseline assessment or the 1-year follow-up increased, the investigators reported (Ann. Rheum. Dis. 2006 Nov. 7 [Epub doi: 10.1136/ard.2006.056390]).

When year 1 HAQ scores were focused on and adjusted for other predictors, the investigators found that functional disability and rheumatoid factor positivity were independent predictors of subsequent early death, including cardiac death, according to the investigators. With each one-point increase in HAQ score, patients had a 48% higher risk of dying within the follow-up period, and a 52% higher risk of dying from cardiovascular disease.

Using HAQ scores obtained at baseline, the investigators found that while disability was a significant risk factor (increasing the risk of all-cause death and cardiovascular disease death by 27% and 15%, respectively, for each 1-point increase in HAQ score), rheumatoid factor positivity was the only independent predictor of all-cause and cardiovascular disease mortality. The investigators repeated the analysis for patients who satisfied ACR criteria for RA by 5 years, and found that the predictive value of 1-year HAQ scores was similar to the predictive value for patients with inflammatory polyarthritis and not RA.

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Color and duplex Doppler ultrasound may be useful in diagnosing ankylosing spondylitis and assessing response to therapy, new data suggest.

Dr. Ercüment Ünlü and colleagues presented data from a study demonstrating that color and duplex Doppler ultrasound can be used to determine the degree of sacroiliitis and spinal inflammation in patients with ankylosing spondylitis (AS).

The study included 39 consecutive patients with AS and 14 healthy, age- and gender-matched controls. Standardized ultrasound settings were applied including color Doppler gain 60–120 dB, wall filter 51–65 Hz, and pulse repetition frequency 300–850 Hz.

Patients with AS had significantly lower resistive index (RI) values in bilateral sacroiliac joints and in lumbar vertebral and thoracal vertebral paraspinal areas than healthy controls. RI is a measure of vascularity, and is expected to be lower in patients with active inflammation because of increased vascularization.

Patients with active disease, according to the Bath AS Disease Activity Index, had significantly higher mean lumbar vertebral and thoracal vertebral RI values (0.820 and 0.789, respectively) than patients with inactive disease (0.863 and 0.825, respectively). The mean RI tended to be lower around the sacroiliac joints in the active group, but the difference was not statistically significant (J. Rheumatol. 2007;34:110–6).

“The difference in spinal inflammation between active and inactive groups was prominent; however the difference in the degree of inflammation of SI [sacroiliac] joints between active and inactive groups became less significant because of the long disease duration of our AS patients,” the authors wrote. The mean disease duration was nearly 10 years.

Among patients with active disease, the ratio of men was significantly higher, as were average erythrocyte sedimentation rates, and C-reactive protein values.

A subset of 11 patients (7 men and 4 women with an average of age 38 years) was administered anti-tumor necrosis factor (TNF) therapy during the study period. Seven patients received infliximab 5 mg/kg IV initially and at week 2, 6, and 12, and four patients received etanercept 25 mg subcutaneous injections twice weekly. Doppler ultrasound measurements were performed at baseline and week 12 of therapy.

After 12 weeks of anti-TNF therapy, there were significant increases from baseline in average sacroiliac RI (0.814 to 0.884) and lumbar vertebral RI (0.821 to 0.883) values, but no significant change in thoracal vertebral RI (0.812 to 0.855), according to the authors from Trakya University Medical Facility in Edirne, Turkey, where the study was conducted.

An editorial accompanying the study called the data interesting, but said it was unfortunate that there was no comparison with MRI findings in the patients and controls (J. Rheumatol. 2007;34:5–7). MRI has been suggested as the best method of detecting sacroiliitis, but practical considerations such as cost and availability limit its use in the clinical setting.

Contrast-enhanced color Doppler ultrasonography has been shown previously to compare favorably with MRI in its ability to demonstrate sacroiliac joint inflammation. Ultrasound is also being used in the area of spondyloarthropathy to detect enthesitis and to assess its response to therapy, according to the editorial.

“The presence or absence of sacroiliitis as detected by whatever reliable, reproducible, and affordable method will continue to be a cornerstone for earlier diagnosis of AS,” the editorial stated. “Doppler ultrasonography may be a useful tool in diagnosing patients with AS and assessing response to therapy.

Further work is definitely warranted in this area.”

Color and duplex Doppler ultrasound may be useful in diagnosing ankylosing spondylitis and assessing response to therapy, new data suggest.

Dr. Ercüment Ünlü and colleagues presented data from a study demonstrating that color and duplex Doppler ultrasound can be used to determine the degree of sacroiliitis and spinal inflammation in patients with ankylosing spondylitis (AS).

The study included 39 consecutive patients with AS and 14 healthy, age- and gender-matched controls. Standardized ultrasound settings were applied including color Doppler gain 60–120 dB, wall filter 51–65 Hz, and pulse repetition frequency 300–850 Hz.

Patients with AS had significantly lower resistive index (RI) values in bilateral sacroiliac joints and in lumbar vertebral and thoracal vertebral paraspinal areas than healthy controls. RI is a measure of vascularity, and is expected to be lower in patients with active inflammation because of increased vascularization.

Patients with active disease, according to the Bath AS Disease Activity Index, had significantly higher mean lumbar vertebral and thoracal vertebral RI values (0.820 and 0.789, respectively) than patients with inactive disease (0.863 and 0.825, respectively). The mean RI tended to be lower around the sacroiliac joints in the active group, but the difference was not statistically significant (J. Rheumatol. 2007;34:110–6).

“The difference in spinal inflammation between active and inactive groups was prominent; however the difference in the degree of inflammation of SI [sacroiliac] joints between active and inactive groups became less significant because of the long disease duration of our AS patients,” the authors wrote. The mean disease duration was nearly 10 years.

Among patients with active disease, the ratio of men was significantly higher, as were average erythrocyte sedimentation rates, and C-reactive protein values.

A subset of 11 patients (7 men and 4 women with an average of age 38 years) was administered anti-tumor necrosis factor (TNF) therapy during the study period. Seven patients received infliximab 5 mg/kg IV initially and at week 2, 6, and 12, and four patients received etanercept 25 mg subcutaneous injections twice weekly. Doppler ultrasound measurements were performed at baseline and week 12 of therapy.

After 12 weeks of anti-TNF therapy, there were significant increases from baseline in average sacroiliac RI (0.814 to 0.884) and lumbar vertebral RI (0.821 to 0.883) values, but no significant change in thoracal vertebral RI (0.812 to 0.855), according to the authors from Trakya University Medical Facility in Edirne, Turkey, where the study was conducted.

An editorial accompanying the study called the data interesting, but said it was unfortunate that there was no comparison with MRI findings in the patients and controls (J. Rheumatol. 2007;34:5–7). MRI has been suggested as the best method of detecting sacroiliitis, but practical considerations such as cost and availability limit its use in the clinical setting.

Contrast-enhanced color Doppler ultrasonography has been shown previously to compare favorably with MRI in its ability to demonstrate sacroiliac joint inflammation. Ultrasound is also being used in the area of spondyloarthropathy to detect enthesitis and to assess its response to therapy, according to the editorial.

“The presence or absence of sacroiliitis as detected by whatever reliable, reproducible, and affordable method will continue to be a cornerstone for earlier diagnosis of AS,” the editorial stated. “Doppler ultrasonography may be a useful tool in diagnosing patients with AS and assessing response to therapy.

Further work is definitely warranted in this area.”

Color and duplex Doppler ultrasound may be useful in diagnosing ankylosing spondylitis and assessing response to therapy, new data suggest.

Dr. Ercüment Ünlü and colleagues presented data from a study demonstrating that color and duplex Doppler ultrasound can be used to determine the degree of sacroiliitis and spinal inflammation in patients with ankylosing spondylitis (AS).

The study included 39 consecutive patients with AS and 14 healthy, age- and gender-matched controls. Standardized ultrasound settings were applied including color Doppler gain 60–120 dB, wall filter 51–65 Hz, and pulse repetition frequency 300–850 Hz.

Patients with AS had significantly lower resistive index (RI) values in bilateral sacroiliac joints and in lumbar vertebral and thoracal vertebral paraspinal areas than healthy controls. RI is a measure of vascularity, and is expected to be lower in patients with active inflammation because of increased vascularization.

Patients with active disease, according to the Bath AS Disease Activity Index, had significantly higher mean lumbar vertebral and thoracal vertebral RI values (0.820 and 0.789, respectively) than patients with inactive disease (0.863 and 0.825, respectively). The mean RI tended to be lower around the sacroiliac joints in the active group, but the difference was not statistically significant (J. Rheumatol. 2007;34:110–6).

“The difference in spinal inflammation between active and inactive groups was prominent; however the difference in the degree of inflammation of SI [sacroiliac] joints between active and inactive groups became less significant because of the long disease duration of our AS patients,” the authors wrote. The mean disease duration was nearly 10 years.

Among patients with active disease, the ratio of men was significantly higher, as were average erythrocyte sedimentation rates, and C-reactive protein values.

A subset of 11 patients (7 men and 4 women with an average of age 38 years) was administered anti-tumor necrosis factor (TNF) therapy during the study period. Seven patients received infliximab 5 mg/kg IV initially and at week 2, 6, and 12, and four patients received etanercept 25 mg subcutaneous injections twice weekly. Doppler ultrasound measurements were performed at baseline and week 12 of therapy.

After 12 weeks of anti-TNF therapy, there were significant increases from baseline in average sacroiliac RI (0.814 to 0.884) and lumbar vertebral RI (0.821 to 0.883) values, but no significant change in thoracal vertebral RI (0.812 to 0.855), according to the authors from Trakya University Medical Facility in Edirne, Turkey, where the study was conducted.

An editorial accompanying the study called the data interesting, but said it was unfortunate that there was no comparison with MRI findings in the patients and controls (J. Rheumatol. 2007;34:5–7). MRI has been suggested as the best method of detecting sacroiliitis, but practical considerations such as cost and availability limit its use in the clinical setting.

Contrast-enhanced color Doppler ultrasonography has been shown previously to compare favorably with MRI in its ability to demonstrate sacroiliac joint inflammation. Ultrasound is also being used in the area of spondyloarthropathy to detect enthesitis and to assess its response to therapy, according to the editorial.

“The presence or absence of sacroiliitis as detected by whatever reliable, reproducible, and affordable method will continue to be a cornerstone for earlier diagnosis of AS,” the editorial stated. “Doppler ultrasonography may be a useful tool in diagnosing patients with AS and assessing response to therapy.

Further work is definitely warranted in this area.”

The patient's twin brother and one sister had been diagnosed with rheumatoid arthritis (RA). On the basis of these findings and the physical evaluation, the primary care physician had diagnosed the man with RA and initiated treatment with nonsteroidal anti-inflammatory agents and prednisone. However, the symptoms did not lessen with treatment.

Physical examination demonstrated dorsal soft-tissue thickening of the bilateral index- and long-finger proximal interphalangeal (PIP) joints, said Dr. Graciela S. Alarcón, the Jane Knight Lowe Chair of Medicine in Rheumatology, in the division of clinical immunology and rheumatology at the University of Alabama, Birmingham. In addition, the patient had severe flexion contractures in the palmar fascia or flexor tendons of both hands—a finding consistent with Dupuytren's contractures. This would explain the man's inability to extend his fingers. Another test for rheumatoid factor was negative and his erythrocyte sedimentation rate was 19 mm/hr.

The presumptive diagnosis included Dupuytren's contracture, a benign, slowly progressive fibroproliferative disease of the palmar fascia that has no clear etiology or pathogenesis, and knuckle pads. The term “knuckle pad” is most often used to describe benign cutaneous lesions of the extensor surfaces of the fingers. However, the lesions most commonly affect the PIP joints rather than the entire extensor surface. These discrete round skin nodules are usually soft and free moving.

Many physicians are unfamiliar with this diagnostic condition; ultrasound examination confirmed the absence of synovitis and the presence of periarticular soft-tissue fullness in this case and several others reported by Dr. Alarcón and her colleagues (Skeletal Radiol. 2006;35:823–7). This may be important to reassure patients and physicians that they are not dealing with RA.

Knuckle pads are commonly associated with palmar and plantar fibromatosis, occurring in up to 20% of patients with Dupuytren's contracture. Less well-defined or softer knuckle pads may be confused with more common causes of soft-tissue swelling, such as inflammatory arthritis. The presence of knuckle pads may lessen the accuracy of the physical exam when assessing the presence of underlying synovitis.

The radiograph shows periarticular soft-tissue fullness, which can sometimes be seen in RA, leaving the diagnosis unclear, said Dr. Robert Lopez, a radiologist at the University of Alabama, Birmingham, who specializes in musculoskeletal imaging.

Ultrasound is demonstrably better than standard clinical joint assessment for synovitis and is more sensitive than radiography in identifying erosive disease in inflammatory arthritis. Another advantage of ultrasound is that it allows physicians to quickly see in the office what the likely causes are, said Dr. Lopez.

In their small series of patients, Dr. Alarcón and Dr. Lopez noted a difference in the sonographic appearance of knuckle pads in patients with and without Dupuytren's in a small series. These two patients showed diffuse areas of lower echo signal and skin thickening overlying the dorsum of the affected PIP joints with a linear hypoechoic band paralleling the epidermis layer. Focal subcutaneous areas of lower echo signal are more suggestive of rheumatoid nodules and neurofibromas.

No sonographic evidence of synovitis was identified in this patient, but there were clear subcutaneous areas of lower echo signal. With arthritis, the joint capsule would appear distended and the cortical surface would be irregular, while the soft tissue would appear normal.

This image shows that “the joint is fine. This person does not have an inflammatory arthritis. What he has is this condition that infiltrates the skin,” said Dr. Lopez.

The patient was reassured that he did not have rheumatoid arthritis, to his relief. He was advised to continue using anti-inflammatories on an as-needed basis but was strongly encouraged not to take them routinely. He was not referred for surgery, because the pads were not causing significant functional impairment and if removed, they are likely to return.

Periarticular soft-tissue fullness is visible on x-ray. Photos couresty Dr. Robert Lopez

Longitudinal ultrasound of the fourth PIP shows diffuse areas of low echo signal.

The patient's twin brother and one sister had been diagnosed with rheumatoid arthritis (RA). On the basis of these findings and the physical evaluation, the primary care physician had diagnosed the man with RA and initiated treatment with nonsteroidal anti-inflammatory agents and prednisone. However, the symptoms did not lessen with treatment.

Physical examination demonstrated dorsal soft-tissue thickening of the bilateral index- and long-finger proximal interphalangeal (PIP) joints, said Dr. Graciela S. Alarcón, the Jane Knight Lowe Chair of Medicine in Rheumatology, in the division of clinical immunology and rheumatology at the University of Alabama, Birmingham. In addition, the patient had severe flexion contractures in the palmar fascia or flexor tendons of both hands—a finding consistent with Dupuytren's contractures. This would explain the man's inability to extend his fingers. Another test for rheumatoid factor was negative and his erythrocyte sedimentation rate was 19 mm/hr.

The presumptive diagnosis included Dupuytren's contracture, a benign, slowly progressive fibroproliferative disease of the palmar fascia that has no clear etiology or pathogenesis, and knuckle pads. The term “knuckle pad” is most often used to describe benign cutaneous lesions of the extensor surfaces of the fingers. However, the lesions most commonly affect the PIP joints rather than the entire extensor surface. These discrete round skin nodules are usually soft and free moving.

Many physicians are unfamiliar with this diagnostic condition; ultrasound examination confirmed the absence of synovitis and the presence of periarticular soft-tissue fullness in this case and several others reported by Dr. Alarcón and her colleagues (Skeletal Radiol. 2006;35:823–7). This may be important to reassure patients and physicians that they are not dealing with RA.

Knuckle pads are commonly associated with palmar and plantar fibromatosis, occurring in up to 20% of patients with Dupuytren's contracture. Less well-defined or softer knuckle pads may be confused with more common causes of soft-tissue swelling, such as inflammatory arthritis. The presence of knuckle pads may lessen the accuracy of the physical exam when assessing the presence of underlying synovitis.

The radiograph shows periarticular soft-tissue fullness, which can sometimes be seen in RA, leaving the diagnosis unclear, said Dr. Robert Lopez, a radiologist at the University of Alabama, Birmingham, who specializes in musculoskeletal imaging.

Ultrasound is demonstrably better than standard clinical joint assessment for synovitis and is more sensitive than radiography in identifying erosive disease in inflammatory arthritis. Another advantage of ultrasound is that it allows physicians to quickly see in the office what the likely causes are, said Dr. Lopez.

In their small series of patients, Dr. Alarcón and Dr. Lopez noted a difference in the sonographic appearance of knuckle pads in patients with and without Dupuytren's in a small series. These two patients showed diffuse areas of lower echo signal and skin thickening overlying the dorsum of the affected PIP joints with a linear hypoechoic band paralleling the epidermis layer. Focal subcutaneous areas of lower echo signal are more suggestive of rheumatoid nodules and neurofibromas.

No sonographic evidence of synovitis was identified in this patient, but there were clear subcutaneous areas of lower echo signal. With arthritis, the joint capsule would appear distended and the cortical surface would be irregular, while the soft tissue would appear normal.

This image shows that “the joint is fine. This person does not have an inflammatory arthritis. What he has is this condition that infiltrates the skin,” said Dr. Lopez.

The patient was reassured that he did not have rheumatoid arthritis, to his relief. He was advised to continue using anti-inflammatories on an as-needed basis but was strongly encouraged not to take them routinely. He was not referred for surgery, because the pads were not causing significant functional impairment and if removed, they are likely to return.

Periarticular soft-tissue fullness is visible on x-ray. Photos couresty Dr. Robert Lopez

Longitudinal ultrasound of the fourth PIP shows diffuse areas of low echo signal.

The patient's twin brother and one sister had been diagnosed with rheumatoid arthritis (RA). On the basis of these findings and the physical evaluation, the primary care physician had diagnosed the man with RA and initiated treatment with nonsteroidal anti-inflammatory agents and prednisone. However, the symptoms did not lessen with treatment.

Physical examination demonstrated dorsal soft-tissue thickening of the bilateral index- and long-finger proximal interphalangeal (PIP) joints, said Dr. Graciela S. Alarcón, the Jane Knight Lowe Chair of Medicine in Rheumatology, in the division of clinical immunology and rheumatology at the University of Alabama, Birmingham. In addition, the patient had severe flexion contractures in the palmar fascia or flexor tendons of both hands—a finding consistent with Dupuytren's contractures. This would explain the man's inability to extend his fingers. Another test for rheumatoid factor was negative and his erythrocyte sedimentation rate was 19 mm/hr.

The presumptive diagnosis included Dupuytren's contracture, a benign, slowly progressive fibroproliferative disease of the palmar fascia that has no clear etiology or pathogenesis, and knuckle pads. The term “knuckle pad” is most often used to describe benign cutaneous lesions of the extensor surfaces of the fingers. However, the lesions most commonly affect the PIP joints rather than the entire extensor surface. These discrete round skin nodules are usually soft and free moving.

Many physicians are unfamiliar with this diagnostic condition; ultrasound examination confirmed the absence of synovitis and the presence of periarticular soft-tissue fullness in this case and several others reported by Dr. Alarcón and her colleagues (Skeletal Radiol. 2006;35:823–7). This may be important to reassure patients and physicians that they are not dealing with RA.

Knuckle pads are commonly associated with palmar and plantar fibromatosis, occurring in up to 20% of patients with Dupuytren's contracture. Less well-defined or softer knuckle pads may be confused with more common causes of soft-tissue swelling, such as inflammatory arthritis. The presence of knuckle pads may lessen the accuracy of the physical exam when assessing the presence of underlying synovitis.

The radiograph shows periarticular soft-tissue fullness, which can sometimes be seen in RA, leaving the diagnosis unclear, said Dr. Robert Lopez, a radiologist at the University of Alabama, Birmingham, who specializes in musculoskeletal imaging.

Ultrasound is demonstrably better than standard clinical joint assessment for synovitis and is more sensitive than radiography in identifying erosive disease in inflammatory arthritis. Another advantage of ultrasound is that it allows physicians to quickly see in the office what the likely causes are, said Dr. Lopez.

In their small series of patients, Dr. Alarcón and Dr. Lopez noted a difference in the sonographic appearance of knuckle pads in patients with and without Dupuytren's in a small series. These two patients showed diffuse areas of lower echo signal and skin thickening overlying the dorsum of the affected PIP joints with a linear hypoechoic band paralleling the epidermis layer. Focal subcutaneous areas of lower echo signal are more suggestive of rheumatoid nodules and neurofibromas.

No sonographic evidence of synovitis was identified in this patient, but there were clear subcutaneous areas of lower echo signal. With arthritis, the joint capsule would appear distended and the cortical surface would be irregular, while the soft tissue would appear normal.

This image shows that “the joint is fine. This person does not have an inflammatory arthritis. What he has is this condition that infiltrates the skin,” said Dr. Lopez.

The patient was reassured that he did not have rheumatoid arthritis, to his relief. He was advised to continue using anti-inflammatories on an as-needed basis but was strongly encouraged not to take them routinely. He was not referred for surgery, because the pads were not causing significant functional impairment and if removed, they are likely to return.

Periarticular soft-tissue fullness is visible on x-ray. Photos couresty Dr. Robert Lopez

Longitudinal ultrasound of the fourth PIP shows diffuse areas of low echo signal.

Combination therapy with disease-modifying antirheumatic drugs in early rheumatoid arthritis is more effective than monotherapy in producing sustained remission, which in turn is associated with better radiographic outcomes, a Finnish study has found.

In a comparison of the rates of achieved and sustained remission and good treatment response among a cohort of early rheumatoid arthritis (RA) patients receiving either combination or single DMARD therapy, patients randomized to combination therapy were more than twice as likely to meet modified American College of Rheumatology (ACR) remission criteria at 2 years and were more than four times as likely to demonstrate sustained remission at each visit, compared with patients on monotherapy, reported Dr. Heidi Makinen of Jyväskylä Central Hospital (Finland) and colleagues in the Finnish RA Combination Therapy Trial (FIN-RACo).

The trial included 169 patients out of 195 included in the original FIN-RACo study for whom complete data were available. Patients were aged 18-65 years and had recent-onset RA, defined as less than 2 years' duration of active disease with 3 or more swollen joints and three of the following: erythrocyte sedimentation rate (ESR) of at least 28 mm/hr or C-reactive protein (CRP) greater than 19 mg/L; morning stiffness lasting a minimum of 29 minutes; more than 5 swollen joints; or more than 10 tender joints.

The 79 patients randomized to combination therapy initially received 500 mg of sulfasalazine twice daily, 7.5 mg methotrexate per week, 300 mg of hydroxychloroquine daily, and 5 mg of prednisolone daily. Dose adjustments were made for patients who did not achieve at least 50% improvement in two of the following three criteria: swollen joint count, tender joint count, and ESR or CRP, and drug replacements were made (auranofin for sulfasalazine or hydroxychloroquine, and azathioprine for methotrexate) if the original agents were discontinued for lack of efficacy or adverse events.

The 90 patients randomized to monotherapy initially received 2 g of sulfasalazine daily, which could be increased up to 3 g per day and, at the discretion of the treating rheumatologist, up to 10 mg of prednisolone daily. In the case of adverse events or lack of efficacy, sulfasalazine could be replaced with methotrexate or another single DMARD. Intra-articular glucocorticoid injections were allowed in all patients at the treating physicians' discretion.

Patient evaluations at baseline, 6, 12, and 24 months included assessments of tender joint count, swollen joint count, duration of morning stiffness, physician and patient overall assessment and pain on visual analog scales, physical function on patient self-report Health Assessment Questionnaire, ESR, and CRP. Radiographs of hands and feet were obtained at 6 and 24 months and were scored by radiologists blinded to the treatments according to the Larsen method.

Remission was defined based on modified ACR criteria, including no joint swelling or soft tissue swelling of tendon sheaths, no joint tenderness or pain on motion, normal ESR, and morning stiffness lasting no longer than 15 minutes. Remission based on Disease Activity Score 28 (DAS28) was defined as a DAS28 score of less than 2.6. Sustained remission was defined as the presence of remission at 6, 12, and 24 months. Good treatment response was defined according to the European League Against Rheumatism (EULAR) treatment response criteria as a DAS28 score less than 3.2 and a decreased DAS28 score of more than 1.2 from baseline.

Of the full study population, 62% were female, 70% were rheumatoid-factor positive, and 48% had evidence of erosions on baseline hand and/or foot radiographs.

Based on the modified ACR criteria, 20 of the combination-therapy patients and 11 of the single-therapy patients were in remission at 6 months. At 12 months, 13 of the combination patients and 3 of the single-therapy patients were still in remission, and at 24 months, 11 of the combination patients and 3 of the single-therapy patients remained in remission. The odds ratio for sustained remission in the combination versus single-therapy group, adjusted for baseline DAS28 values, was 4.61, the authors reported (J. Rheumatol. 2007;34:1–6).

With respect to the duration of DAS28 remission, 52 of the combination patients were in DAS28 remission at 6 months, and 45 and 40 were still in DAS28 remission at 12 and 24 months, respectively. In the single-therapy group, 33 patients were in DAS28 remission at 6 months, and 21 and 14 remained in DAS28 remission at months 12 and 24, respectively. As such, the odds ratio for sustained DAS28 remission in the combination-therapy group, compared with the single-therapy group was 5.58, the authors wrote.

Treatment responses were good based on the EULAR criteria in 59 of the combination patients and 47 of the single-therapy patients at 6 months. Approximately 67% of the combination patients and 27% of the single-therapy patients demonstrated sustained good responses at 24 months, they stated.

A review of the association between radiographic progression and the sustained remission and good treatment response showed markedly less deterioration in Larson score among patients in sustained remission, compared with those who achieved remission at the 6-month visit but did not sustain it, according to the investigators. Because sustained remissions were more common in the combination-therapy patients, it follows that such treatment would be associated with better radiographic outcomes, they said.

While the study was limited by its assessment of remission only at the 6-, 12-, and 24-month time points—leaving open the possibility that patients in remission at those time points could have experienced active disease flares between visits—previous studies have shown that such flares are often linked to discontinuation of therapy while in remission. “In our study, combination therapy was continued successfully for 2 years, and half the patients remained in sustained DAS28 remission,” the authors wrote.

The findings of this study suggest that sustained remission, rather than remission, should be the goal of DMARD therapy, the authors concluded.

Combination therapy with disease-modifying antirheumatic drugs in early rheumatoid arthritis is more effective than monotherapy in producing sustained remission, which in turn is associated with better radiographic outcomes, a Finnish study has found.

In a comparison of the rates of achieved and sustained remission and good treatment response among a cohort of early rheumatoid arthritis (RA) patients receiving either combination or single DMARD therapy, patients randomized to combination therapy were more than twice as likely to meet modified American College of Rheumatology (ACR) remission criteria at 2 years and were more than four times as likely to demonstrate sustained remission at each visit, compared with patients on monotherapy, reported Dr. Heidi Makinen of Jyväskylä Central Hospital (Finland) and colleagues in the Finnish RA Combination Therapy Trial (FIN-RACo).

The trial included 169 patients out of 195 included in the original FIN-RACo study for whom complete data were available. Patients were aged 18-65 years and had recent-onset RA, defined as less than 2 years' duration of active disease with 3 or more swollen joints and three of the following: erythrocyte sedimentation rate (ESR) of at least 28 mm/hr or C-reactive protein (CRP) greater than 19 mg/L; morning stiffness lasting a minimum of 29 minutes; more than 5 swollen joints; or more than 10 tender joints.

The 79 patients randomized to combination therapy initially received 500 mg of sulfasalazine twice daily, 7.5 mg methotrexate per week, 300 mg of hydroxychloroquine daily, and 5 mg of prednisolone daily. Dose adjustments were made for patients who did not achieve at least 50% improvement in two of the following three criteria: swollen joint count, tender joint count, and ESR or CRP, and drug replacements were made (auranofin for sulfasalazine or hydroxychloroquine, and azathioprine for methotrexate) if the original agents were discontinued for lack of efficacy or adverse events.

The 90 patients randomized to monotherapy initially received 2 g of sulfasalazine daily, which could be increased up to 3 g per day and, at the discretion of the treating rheumatologist, up to 10 mg of prednisolone daily. In the case of adverse events or lack of efficacy, sulfasalazine could be replaced with methotrexate or another single DMARD. Intra-articular glucocorticoid injections were allowed in all patients at the treating physicians' discretion.

Patient evaluations at baseline, 6, 12, and 24 months included assessments of tender joint count, swollen joint count, duration of morning stiffness, physician and patient overall assessment and pain on visual analog scales, physical function on patient self-report Health Assessment Questionnaire, ESR, and CRP. Radiographs of hands and feet were obtained at 6 and 24 months and were scored by radiologists blinded to the treatments according to the Larsen method.

Remission was defined based on modified ACR criteria, including no joint swelling or soft tissue swelling of tendon sheaths, no joint tenderness or pain on motion, normal ESR, and morning stiffness lasting no longer than 15 minutes. Remission based on Disease Activity Score 28 (DAS28) was defined as a DAS28 score of less than 2.6. Sustained remission was defined as the presence of remission at 6, 12, and 24 months. Good treatment response was defined according to the European League Against Rheumatism (EULAR) treatment response criteria as a DAS28 score less than 3.2 and a decreased DAS28 score of more than 1.2 from baseline.

Of the full study population, 62% were female, 70% were rheumatoid-factor positive, and 48% had evidence of erosions on baseline hand and/or foot radiographs.

Based on the modified ACR criteria, 20 of the combination-therapy patients and 11 of the single-therapy patients were in remission at 6 months. At 12 months, 13 of the combination patients and 3 of the single-therapy patients were still in remission, and at 24 months, 11 of the combination patients and 3 of the single-therapy patients remained in remission. The odds ratio for sustained remission in the combination versus single-therapy group, adjusted for baseline DAS28 values, was 4.61, the authors reported (J. Rheumatol. 2007;34:1–6).

With respect to the duration of DAS28 remission, 52 of the combination patients were in DAS28 remission at 6 months, and 45 and 40 were still in DAS28 remission at 12 and 24 months, respectively. In the single-therapy group, 33 patients were in DAS28 remission at 6 months, and 21 and 14 remained in DAS28 remission at months 12 and 24, respectively. As such, the odds ratio for sustained DAS28 remission in the combination-therapy group, compared with the single-therapy group was 5.58, the authors wrote.

Treatment responses were good based on the EULAR criteria in 59 of the combination patients and 47 of the single-therapy patients at 6 months. Approximately 67% of the combination patients and 27% of the single-therapy patients demonstrated sustained good responses at 24 months, they stated.

A review of the association between radiographic progression and the sustained remission and good treatment response showed markedly less deterioration in Larson score among patients in sustained remission, compared with those who achieved remission at the 6-month visit but did not sustain it, according to the investigators. Because sustained remissions were more common in the combination-therapy patients, it follows that such treatment would be associated with better radiographic outcomes, they said.

While the study was limited by its assessment of remission only at the 6-, 12-, and 24-month time points—leaving open the possibility that patients in remission at those time points could have experienced active disease flares between visits—previous studies have shown that such flares are often linked to discontinuation of therapy while in remission. “In our study, combination therapy was continued successfully for 2 years, and half the patients remained in sustained DAS28 remission,” the authors wrote.

The findings of this study suggest that sustained remission, rather than remission, should be the goal of DMARD therapy, the authors concluded.

Combination therapy with disease-modifying antirheumatic drugs in early rheumatoid arthritis is more effective than monotherapy in producing sustained remission, which in turn is associated with better radiographic outcomes, a Finnish study has found.

In a comparison of the rates of achieved and sustained remission and good treatment response among a cohort of early rheumatoid arthritis (RA) patients receiving either combination or single DMARD therapy, patients randomized to combination therapy were more than twice as likely to meet modified American College of Rheumatology (ACR) remission criteria at 2 years and were more than four times as likely to demonstrate sustained remission at each visit, compared with patients on monotherapy, reported Dr. Heidi Makinen of Jyväskylä Central Hospital (Finland) and colleagues in the Finnish RA Combination Therapy Trial (FIN-RACo).

The trial included 169 patients out of 195 included in the original FIN-RACo study for whom complete data were available. Patients were aged 18-65 years and had recent-onset RA, defined as less than 2 years' duration of active disease with 3 or more swollen joints and three of the following: erythrocyte sedimentation rate (ESR) of at least 28 mm/hr or C-reactive protein (CRP) greater than 19 mg/L; morning stiffness lasting a minimum of 29 minutes; more than 5 swollen joints; or more than 10 tender joints.

The 79 patients randomized to combination therapy initially received 500 mg of sulfasalazine twice daily, 7.5 mg methotrexate per week, 300 mg of hydroxychloroquine daily, and 5 mg of prednisolone daily. Dose adjustments were made for patients who did not achieve at least 50% improvement in two of the following three criteria: swollen joint count, tender joint count, and ESR or CRP, and drug replacements were made (auranofin for sulfasalazine or hydroxychloroquine, and azathioprine for methotrexate) if the original agents were discontinued for lack of efficacy or adverse events.

The 90 patients randomized to monotherapy initially received 2 g of sulfasalazine daily, which could be increased up to 3 g per day and, at the discretion of the treating rheumatologist, up to 10 mg of prednisolone daily. In the case of adverse events or lack of efficacy, sulfasalazine could be replaced with methotrexate or another single DMARD. Intra-articular glucocorticoid injections were allowed in all patients at the treating physicians' discretion.

Patient evaluations at baseline, 6, 12, and 24 months included assessments of tender joint count, swollen joint count, duration of morning stiffness, physician and patient overall assessment and pain on visual analog scales, physical function on patient self-report Health Assessment Questionnaire, ESR, and CRP. Radiographs of hands and feet were obtained at 6 and 24 months and were scored by radiologists blinded to the treatments according to the Larsen method.

Remission was defined based on modified ACR criteria, including no joint swelling or soft tissue swelling of tendon sheaths, no joint tenderness or pain on motion, normal ESR, and morning stiffness lasting no longer than 15 minutes. Remission based on Disease Activity Score 28 (DAS28) was defined as a DAS28 score of less than 2.6. Sustained remission was defined as the presence of remission at 6, 12, and 24 months. Good treatment response was defined according to the European League Against Rheumatism (EULAR) treatment response criteria as a DAS28 score less than 3.2 and a decreased DAS28 score of more than 1.2 from baseline.

Of the full study population, 62% were female, 70% were rheumatoid-factor positive, and 48% had evidence of erosions on baseline hand and/or foot radiographs.

Based on the modified ACR criteria, 20 of the combination-therapy patients and 11 of the single-therapy patients were in remission at 6 months. At 12 months, 13 of the combination patients and 3 of the single-therapy patients were still in remission, and at 24 months, 11 of the combination patients and 3 of the single-therapy patients remained in remission. The odds ratio for sustained remission in the combination versus single-therapy group, adjusted for baseline DAS28 values, was 4.61, the authors reported (J. Rheumatol. 2007;34:1–6).

With respect to the duration of DAS28 remission, 52 of the combination patients were in DAS28 remission at 6 months, and 45 and 40 were still in DAS28 remission at 12 and 24 months, respectively. In the single-therapy group, 33 patients were in DAS28 remission at 6 months, and 21 and 14 remained in DAS28 remission at months 12 and 24, respectively. As such, the odds ratio for sustained DAS28 remission in the combination-therapy group, compared with the single-therapy group was 5.58, the authors wrote.

Treatment responses were good based on the EULAR criteria in 59 of the combination patients and 47 of the single-therapy patients at 6 months. Approximately 67% of the combination patients and 27% of the single-therapy patients demonstrated sustained good responses at 24 months, they stated.

A review of the association between radiographic progression and the sustained remission and good treatment response showed markedly less deterioration in Larson score among patients in sustained remission, compared with those who achieved remission at the 6-month visit but did not sustain it, according to the investigators. Because sustained remissions were more common in the combination-therapy patients, it follows that such treatment would be associated with better radiographic outcomes, they said.

While the study was limited by its assessment of remission only at the 6-, 12-, and 24-month time points—leaving open the possibility that patients in remission at those time points could have experienced active disease flares between visits—previous studies have shown that such flares are often linked to discontinuation of therapy while in remission. “In our study, combination therapy was continued successfully for 2 years, and half the patients remained in sustained DAS28 remission,” the authors wrote.

The findings of this study suggest that sustained remission, rather than remission, should be the goal of DMARD therapy, the authors concluded.